Download AN INTERNET DATABASE ON GENETIC NON

INFOLETTER 4
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LOOK UP THE H.E.A.R. HOMEPAGE!
At
http://hear.unife.it
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THE HEREDITARY HEARING LOSS HOMEPAGE
Guy Van Camp1, Richard J.H. Smith2
1
Department of Medical Genetics, University of Antwerp, Belgium
2
Molecular Otolaryngology Research Labs, Department of Otolaryngology, University of
Iowa, Iowa City
Until four years ago, advances in the field of non-syndromal hereditary hearing impairment
(NSHI) remained very modest in comparison with other genetic diseases. In 1988, the first
locus for NSHI was discovered on the X-chromosome (Wallis et al 1988, Brunner et al, 1988).
Deafness in these families is characterised by congenital mixed conductive and perceptive
hearing impairment. Affected persons also have stapes fixation and an abnormal
communication between the cerebrospinal fluid and perilymph, which may cause leakage
during ear surgery (perilymphatic gusher). Due to these additional structural abnormalities,
these persons form an identifiable subgroup among persons with NSHI. A number of affected
persons have been studied and in many, microdeletions have been found that defined a small
chromosomal interval containing the deafness gene. Not surprisingly, in 1995, this gene
became the first gene for NSHI to be discovered (de Kok et al, 1995). Identified as the
POU3F4 gene, it is an important transcription factor in embryonic development.
In 1992, the second NSHI locus was mapped in a large Costa Rican family with autosomal
dominant progressive NSHI starting in the low tones during childhood (Léon et al, 1992).
Although several other large families with postlingual NSHI had been described in the '60s
and '70s, only after the impetus provided by Léon were these families analysed by linkage
analysis. The hearing impairment in nearly all is postlingual and progressive, and the
inheritance pattern, autosomal dominant. However, other types of inheritance were noted, and
in 1993, the maternal inheritance of a mitochondrial mutation leading to NSHI was reported in
an Arab-Israeli pedigree (Prezant et al, 1993). Interestingly, this mutation also was found in
persons with aminoglycoside-induced hearing loss. This association exists because the
mutation occurs in the mitochondrial small subunit ribosomal RNA (ssrRNA) gene, a gene
highly homologous to its bacterial ssrRNA counterpart, at the binding site of aminoglycosides
in bacteria.
It was not until 1994 that the first loci for autosomal recessive NSHI were identified.
Although ascertainment was not problematic as the usual phenotype is congenital prelingual
severe-to-profound hearing impairment, the reasons for this delay were significant genetic
heterogeneity and assortative mating. In most of the pedigrees with prelingual deafness from
the Western world, several deaf individuals have intermarried and introduced different
deafness genes into these families, precluding simple genetic analysis. However, families
from ethnic isolates proved to be invaluable, and linkage analyses were very successful. Only
a single nuclear consanguineous family with multiple affected progeny was necessary to map
a locus for autosomal recessive NSHI.
Over the past 4 years the number of NSHI genes that have been localised has expanded
greatly. In 1994, 6 new loci were discovered - the first two loci for autosomal recessive NSHI,
the second and third locus for autosomal dominant NSHI, and a second mitochondrial
mutation. Forty loci have now been reported. This list includes 8 X-linked, 13 dominant, 17
recessive, and 2 mitochondrial loci. X-linked loci are given the prefix "DFN" (the
abbreviation for non-syndromic hearing impairment); autosomal dominant loci, "DFNA"; and,
autosomal recessive loci, "DFNB”. The prefix is followed by a number to reflect the
sequential order of discovery. However, this numbering system is not always exactly in the
order of discovery, especially for the X-linked loci. For example, the first X-linked locus for
NSHI is named DFN3 because the names DFN1 and DFN2 had been previously assigned,
though incorrectly. DFN1 had been given to a form of X-linked deafness that is really a
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syndromal form of deafness, and DFN2 had been attributed to X-linked congenital profound
deafness in families in which linkage had not been established. Recently, however, the DFN2
locus has been mapped to Xq22 (Tyson et al, 1996). Despite the large number of NSHI gene
localisation’s, the number of genes that have been identified remains small. In addition to the
POU3F4 gene, only two other NSHI genes have been reported. Mutations in the
unconventional myosin VIIA lead to DFNB2 (Weil et al, 1997; Liu et al, 1997) as well as
Usher syndrome type 1b (Weil et al, 1996), and mutations in Gap Junction protein, beta-2
(GJB2; also known as Connexin 26, Cx26) cause DFNB1 and DFNA3. Unconventional
myosins are transport proteins containing structurally conserved heads that serve as motors
and divergent cargo-specific tails. Gap junctions are plasma membrane channels that form
hexameric subunit proteins called connexons to facilitate the exchange of molecules up to 1
kDA between cells.
In 1994-95, as the number of reported NSHI loci quickly increased, it became apparent that a
rapid means of exchange of information was needed to avoid confusion in nomenclature. In
November, 1995, a list of known loci for NSHI with their DFN number was placed on the
Internet under the name Hereditary Hearing loss Homepage. Although initially a simple table
containing locus names, cytogenetic localisation’s, screening markers and references, the
resource has grown to include various other types of information, such as data about linked
families and candidate regions, addresses, information on cloned genes, links to other
databases, syndromal hearing impairment, and mouse models. As the developers of this
resource, we look forward to its continued growth in order to provide up-to-date information
to the hereditary hearing impairment research community.
References
Brunner H, Bennekom C, Lambermon E, Oei L, Cremers C, Wieringa B, Ropers H (1988)
The gene for X-linked progressive deafness with perilymphatic gusher during surgery
(DFN3) is linked to PGK. Hum Genet 80:337-340
de Kok YJM, van der Maarel SM, Bitner-Glindzicz M, Huber I, Monaco AP, Malcolm S,
Pembrey ME et al. (1995) Association between X-linked mixed deafness and mutations in
the POU domain gene POU3F4. Science 267: 685-688
Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, Mueller RF, Leigh IM
(1997) connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature
387:80-83
Léon PE, Raventos H, Lynch E, Morrow J, King M-C (1992) The gene for an inherited form
of deafness maps to chromosome 5q31. Proc Natl Acad Sci USA 89:5181-5184
Liu XZ, Walsh J, Mburu P, Kendrick-Jones J, Cope MJTV, Steel KP, Brown, SDM (1997)
Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nature Genet
16:188-190
Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, Arnos KS et al. (1993)
Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and
non-syndromic deafness. Nature Genet 4:289-294
Tyson J, Bellman S, Newton V, Simpson P, Malcolm S, Pembrey M E, Bitner-Glindzicz M
(1996) Mapping of DFN2 to Xq22. Hum Mol Genet 5:2055-2060
Wallis C, Ballo R, Wallis G, Beighton P, Goldblatt J (1988) X-linked mixed deafness with
stapes fixation in a Mauritian kindred: linkage to Xq probe pDP34. Genomics 3:299-301
Weil D, Blanchard S, Kaplan J, Guilford P, Gibson F, Walsh J, Mburu P et al. (1995)
Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature 374:60-61
Weil D, Kussel P, Blanchard S, Levy G, Levi-Acobas F, Drira M, Ayadi H, Petit C (1997)
The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic
defects of the myosin-VIIA gene. Nature Genet 16:191-193
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The Hereditary Hearing loss Homepage can be reached at the following URL address:
http://dnalab-www.uia.ac.be/dnalab/hhh/
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FIG.1
FIG 2
TAB. 1,2,3,4,5,6,7
Legends to figures
Figure 1: Number of gene localizations for non-syndromic hearing impairment in the last
years.
Figure 2: Index page of the Hereditary Hearing loss Homepage. For each of the items that are
underlined, separate pages are available that contain more detailed information.
Table 1: Non-syndromic hearing impairment. Gene localizations identified for Autosomal
dominant diseases (from the Hereditary Hearing loss Homepage).
Table 2: Non-syndromic hearing impairment. Gene localizations identified for Autosomal
recessive diseases (from the Hereditary Hearing loss Homepage).
Table 3: Non-syndromic hearing impairment. Gene localizations identified for X-linked
diseases (from the Hereditary Hearing loss Homepage).
Table 4: Non-syndromic hearing impairment. Gene localizations identified for mithocondrial
diseases (from the Hereditary Hearing loss Homepage).
Table 5: Syndromic hearing impairment. Gene localizations identified for Syndromic diseases
(from the Hereditary Hearing loss Homepage).
Table 6: Syndromic hearing impairment. Gene localizations identified for Usher syndrome
(from the Hereditary Hearing loss Homepage).
Table 7: Syndromic hearing impairment. Gene localizations identified Waardenburg
syndrome (from the Hereditary Hearing loss Homepage).
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INTERNET DATABASE ON GENETIC NON-SYNDROMAL HEARING
IMPAIRMENTS
Manuela Mazzoli1, Leopoldo Saggin2, Stavros Hatzopoulos1, Alessandro Martini1
1
2
Servizio di Audiologia, Università di Ferrara, Italy
Centro Informatico Vallisneri, Dipartimento di Biologia, Università di Padova, Italy
The scarcity of affected families available in a certain area, or city is often an obstacle to
research on the genetics of non-syndromal hearing impairments (NSHI). This was one of the
reasons why several research groups decided to join forces and establish a European
Concerted Action on Genetics of Hearing Impairment (H.E.A.R.) to co-ordinate research and
progress in this field. In order to circulate information and collect European-based data, an
information retrieval system (IRS) from a database of families with genetic NSHI has been
designed. The suggestion for a database came from the consideration that most hereditary
hearing impairments are rare and it is difficult to find affected families, especially those which
are large enough to allow linkage studies. Furthermore, the database would facilitate the
standardised collection of data using common terminology, definitions and testing as well as
being a reference source for information and for comparison of clinical descriptions: with data
from other groups. Finally, it could represent, in time, a repository of European
epidemiological data. Since the use of informatics resources and the possibility of connecting
with the Internet is increasing rapidly, we investigated the possibility of using the World Wide
Web (WWW) as a simple and standardised system to make data easily available to interested
users anywhere in the world.
One of the aims of the Concerted Action is to create common working platforms which are
available to different groups involved in the research and the Internet seems to be the most
appropriate environment to do this. In fact, other Concerted Action members have already
designed Home Pages which contain information relating to research on the genetics of
hearing impairment, such as the Hereditary Hearing Homepage designed at the Department of
Medical Genetics of the University of Antwerp1. Another site may be found on the Net for
collection of data about families with hereditary hearing impairment: the National Institute on
Deafness and Other Communication Disorders (NIDCD) Hereditary Hearing Impairment
Resource Registry2 In the latter, a research plan is presented, but data are not accessible. For
the present work it is intended to create a working platform to allow researchers to work on a
common basis, although in different countries.
The IRS presented here will be linked to these and other relevant Internet sites. It is hoped that
this IRS will represent an easy-to-use tool to increase information exchange, to file data in a
standardised manner, and to retrieve information for research, statistics, or clinical use,
anywhere in the world.
In order to create an IRS for genetic hearing impairment the design of the database structure
had to be considered in terms of fields composition of the records in the database. Moreover,
suitable software had to be selected in order to index table of this database.
It was decided to use an IRS because: 1) there are many reliable Information Retrieval free
packages downloadable from the net while there a free database engine is still lacking; 2) IRS
reduces the possibility of human error in loading data to the database, since data input relies
on one or few persons. The different fields were defined according to definitions that were
agreed upon during European Working Group meetings and that have been published in
Infoletter 23.
The aim of this project is however the evolution from an IRS to a true database, i.e. a system
where each user can not only search data, but also input or modify its own contributed data.
Such a system presents the advantage of having the information “on-line”. In this case one of
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the main problem to solve when designing the database is guarantee the security of data, so
that information cannot be modified by users other than the researcher that originally
presented the information.
Another problem is the choice of the database engine. At now, there is a lot of effort aimed to
the development of free database engines searchable through World Wide Web and the
definition of some standards is likely in a very short time.
The query form and data submission forms of the IRS as well as the “help” explanatory
sections are illustrated in details in Appendix 1, so that interested researchers may contribute
in sending information on cases studied in their institutions, clinics and laboratories. If the
access to the Internet is not available to some, there is still the possibility to send the
information through the fax form. We believe it is of extreme importance to send as much
information as possible in order to fulfil one of the aims of the Concerted Action to collect
European based data. It could also justify a continuation of the project and the presentation of
an application for funding renewal.
REFERENCES
(1) http://dnalab-www.uia.ac.be/dnalab/hhh/index.html
(2) http://www.boystown.org/hhirr/hhirr.htm
(3) Infoletter: edited by European Work Group on Gentics of Hearing Impairment, vol. 2,
November, 1996.
The Genetic hearing impairment - Family database can be reached at the following URL
address:
http://hear.unife.it/audiology/index
NOTE: to send data (not to query the database) a login and password are needed. This
is for security of data and to avoid unreal data to be sended to the database. Please, for
more information about this, contact:
Manuela Mazzoli, MD
Servizio di Audiologia
Ospedale S.Anna
Corso Giovecca 203
44100 FERRARA - ITALY
Voice: +39 (532) 295.341
Fax: +39 (532) 295.887
E-mail: [email protected]
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Appendix 1
Help For Data Submission
You can contribute with your data to "Family Databases" using one of the following
methods, sorted in descending order of preference:
1. Compiling the Family Database Submission Form via www
NOTE: This is a login + password restricted site for the Members of the H.E.A.R.
Concerted Action.
If you do not know the login and password, as proposed at the Ferrara
Meeting, October 10-12, 1997, please e-mail to the H.E.A.R. Database
Administrator: [email protected]
You have to fill in a form for each family you want to submit.
Please note that if you are re-submitting data referring to an already filed family, then you
have to report this in an e-mail to the H.E.A.R. Database Administrator containing the
FAMILY CODE of the family to be substituted. If you want a detailed help on how to fill in
the WWW Submission Form follow this link.
2. Asking for the Faxable Submission Form to:
Manuela Mazzoli, MD
Servizio di Audiologia
Ospedale S.Anna
Corso Giovecca 203
44100 FERRARA - ITALY
Voice: +39 (532) 295.341
Fax: +39 (532) 295.887
E-mail: [email protected]
You can also get the Faxable Submission Form directly from the Internet, following this
link.
NOTE: This is also a login + password restricted site for the Members of the
H.E.A.R. Concerted Action.
If you do not know the login and password, as proposed at the Ferrara
Meeting, October 10-12, 1997, please e-mail to the H.E.A.R. Database
Administrator.
If you get Faxable Submission Form directly from the Internet, then you have to print this
form on your printer, compile and send it by fax.
You have to fill in a form for each family you want to submit.
Please note that if you are re-submitting data referring to an already filed family, then you
have to report this in an accompanying sheet. If you want a detailed help on how to fill in the
Faxable Submission Form follow this link.
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Help for Data Submission via WWW
A. General Warnings
The first requirement is: please fill in all the fields of the form. If you do not want to fill in
some fields, please leave to their default values. There are also special rules for each field that
are reported below. The second requirement is: free-text fields can contain only pure ASCII
characters, i.e. A-Z, a-z, 0-9, + (plus), - (minus), _ (underscore) ,'(apostrophe). So, please do
not use language-specific characters like umlaut, accented characters etc... If you have an
accent at the end of a word then you must use the character ' (ASCII 39) instead. Please, don't
use accented characters inside terms!!! Our database is not suited to handle these particular
characters! On the contrary, you can use apostrophes (for example: O'Neil).
B. What If The Family Was Already Filed, But Some Data Are Changed Since Then?
In this case, please send an e-mail to H.E.A.R. Database Administrator reporting this fact. In
the letter specify the FAMILY CODE of the family to be substituted. Thank you!
C. What If the Family Presents with Heterogeneous Data?
Some fields CAN contain more than one term. Suppose you have a family where there are
persons with different hearing impairment e.g. some people present with moderate hearing
impairment and others with severe, then you will select more than a term for that field.
Fields supporting this possibility are described below.
D. Rules For Filling In Each Field
1. FAMILY CODE
To respect patients' privacy you should give a family a code. This is a 13 characters field
whose content MUST follow these rules:
1. The first two characters are the tag of the country where the principal investigator comes
from. They MUST be Upper Case. Internet rules are followed (for example: IT=Italy,
SE=Sweden, DE=Germany, UK=United Kingdom, FR=France, ES=Spain,
BE=Belgium, NL=The Netherlands etc...).
2. The 3rd character must be an _ (underscore)
3. Characters # 4-6 must be three Upper Case characters that are an ID of the principal
investigator (for example: MMA is for Martini Alessandro)
4. The 7th character must be an _ (underscore)
5. Characters # 8-9 are OT (Upper case) for Otosclerosis or NS (Upper Case) for Non
Syndromic kind of impairment
6. The 10th character must be an _ (underscore)
7. Characters # 11-13 are a "three number tag" that is a progressive id for the family
discovered by an investigator. This way a maximum of 999 families for each principal
investigator is allowed. Numbers <100 must prefixed with zeros (e.g. 003, 027 etc...).
This is an example of how a FAMILY CODE must be written:
IT_MMA_OT_001
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This means that this is a family with Otosclerosis (OT) filed as #1 (001) in the records of Dr.
Alessandro Martini (MMA) in Italy (IT).
2. RESEARCHER
Fill in input box with data. No particular rule must be followed.
3. INSTITUTION
Fill in input box with data. No particular rule must be followed.
4. ADDRESS
Fill in input box with data. No particular rule must be followed.
5. E-MAIL
Input your e-mail address into the box. In the remote evenience ;-) you can access WWW but
you do not have an e-mail address, please leave this to its default value.
6. CITY
Fill in input box with data. No particular rule must be followed. Keep in mind that CITY field
includes also the ZIP code.
7. COUNTRY
Fill in input box with data. No particular rule must be followed.
8. INHERITANCE
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a radio button selection, i.e. you
can choose only one term.
9. FREQUENCY IMPAIRMENT
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a checkbox button selection, i.e.
you can choose one or more terms if more than a condition is present inside the family. The
criteria for selecting different options are the following:
* Low: <= 500 Hz frequency ranges impairment
* Mid: 501 - 2000 Hz frequency ranges impairment
* High: > 2000 Hz frequency ranges impairment
10. HEARING LEVELS IMPAIRMENT
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a checkbox button selection, i.e.
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you can choose one or more terms if more than a condition is present inside the family. The
criteria for selecting different options are the following:
Mild
Reduction < 40dB. Average across 500, 1000, 2000 and 4000Hz (PTA) of the better
hearing ear.
Moderate Reduction of 40-69dB. Average across 500, 1000, 2000 and 4000Hz (PTA) of the
better hearing ear.
Severe Reduction of 70-94dB. Average across 500, 1000, 2000 and 4000Hz (PTA) of the
better hearing ear.
Profound Reduction >=95dB. Average across 500, 1000, 2000 and 4000Hz (PTA) of the
better hearing ear.
11. TINNITUS
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a radio button selection, i.e. you
can choose only one term.
12. TYPE
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a radio button selection, i.e. you
can choose only one term.
13. ONSET
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a checkbox button selection, i.e.
you can choose one or more terms if more than a condition is present inside the family.
14. PROGRESSION
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a checkbox button selection, i.e.
you can choose one or more terms if more than a condition is present inside the family.
15. LATERALISATION
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a checkbox button selection, i.e.
you can choose one or more terms if more than a condition is present inside the family.
16. VESTIBULAR ACTIVITY
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a checkbox button selection, i.e.
you can choose one or more terms if more than a condition is present inside the family.
17. RADIOLOGICAL MALFORMATIONS
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The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a checkbox button selection, i.e.
you can choose one or more terms if more than a condition is present inside the family.
18. CONSANGUINEITY
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a radio button selection, i.e. you
can choose only one term.
19. RACE
The possible content of this field is one of the terms reported in the list aside. Select the
button on the left of the term chosen. Please note that this is a radio button selection, i.e. you
can choose only one term.
20. GEOGRAPHIC ORIGIN
This is where the family come from. This is not a searchable field so in principle could be
narrowed down to a single village :) No particular rule must be followed.
21. PRESENTATION
The possible content of this field is homogeneous or heterogeneous. This second term refers
to intrafamilial differences in phenotype (e.g. different frequency ranges impaired or different
levels of impairment within the family). Please note that this is a radio button selection, i.e.
you can choose only one term.
22. HEREDITARY TREE
Please DO NOT fill in this field!!!
We'll do it for you, if you send us an image of hereditary tree. See the instructions below.
23. AFFECTED
Fill in the input box with the arabic number of subjects affected in the family under study.
For otosclerotic families type the number of the affected members under study and, within
brackets, the character + (plus) and the number of subjects with:
1. Normal hearing and absence of stapedial refexes
2. Stapedial refexes with the on-off effect
For example: 5 (+3)
24. GENERATIONS
Fill in the input box with the arabic number of generation(s) available in the family under
study.
25. GeneLOCALISATION
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Specify if known, otherwise leave the input box with the default value, i.e. Unknown.
26. GeneID
Specify if known, otherwise leave the input box with the default value, i.e. Unknown.
27. CHROMOSOME
Specify if known, otherwise leave the input box with the default value, i.e. Unknown.
28. MUTATION
Specify if known, otherwise leave the input box with the default value, i.e. Unknown.
29. PHENOTYPE
Please DO NOT fill in this field!!!
It will become an hyperlink to the phenotype database when more information about mutation
loci and phenotypes will be available.
30. NOTES
In this field you can add notes if useful to characterise the family (e.g. brief description of Rx
Malformations). You can continue to input characters overriding the right border of the input
box.
E . Processing The Form
When you have filled in ALL the fields, you can submit the form by clicking the Submit Form
button. Whenever you want BEFORE clicking Submit Form button, you can change your
mind and RESET the form to the default (initial) values, by clicking the Reset Form button.
After the submission, a copy of data just sent appear on the screen, if everything is correct.
Please check it!!!. If some data was wrong, please send immediately an e-mail to the H.E.A.R.
Database Administrator explaining what was wrong or asking for not processing data at all.
If the filling in of the form was incomplete or incorrect, an ERROR page appears explaining
what was wrong or what lacks. In this last case you can go back to your form and complete it.
Then you can try to submit it again.
F. Image of The Hereditary Tree
You can also send optionally an image of the hereditary pattern of transmission of the hearing
impairment inside a family. The name of the files MUST follow the rules of DOS filenames,
i.e. 8 characters for the filename, a dot --> '.'and an extension of 3 characters. The name of the
file is basically the same use for the Family Code, i.e.:
1. Characters # 1-3 must be three characters that are an ID of the principal investigator (for
example: MMA is for Martini Alessandro)
2. Characters # 4-5 are OT for Otosclerosis or NS for Non Syndromic kind of impairment
3. Characters # 6-8 are a "three number tag" that is a progressive id for the family
discovered by an investigator.
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4. The extension (the part of the filename after the dot) should be JPG or GIF depending
on the graphics format chosen.
This is an example of how to name a hereditary tree image: MMAOT001.GIF
This means that this is the hereditary tree image of the family whose code was
IT_MMA_OT_001.
To send images you can:
1. Send a 16 colours .GIF or .JPG image not exceeding 400 (x axis) x 300 (y axis) pixels as
e-mail attachment to Hear Database Administrator. Please, use the MIME or BinHex type
of encoding to send data, NOT the uuencode method!
2. Send a good quality image of the hereditary tree by mail or by fax to:
Dr. M. Mazzoli
Servizio di Audiologia
Ospedale S. Anna
Corso Giovecca 203
44100 FERRARA - ITALY
Voice: +39 (532) 29-5407
Fax: +39 (532) 29-5887
E-mail: [email protected]
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Help For Data Submission via Fax
A. General Warnings
Once you have got your Faxable Submission Form, you can fill in it. The criteria to to be used
are reported below.
1. Data MUST contain only pure ASCII characters, i.e. A-Z, a-z, 0-9, + (plus), - (minus), _
(underscore) ,'(apostrophe). So, please do not use language-specific characters like umlaut,
accented characters etc... If you have an accent at the end of a word then you must use the
character ' (ASCII 39) instead. Please, don't use accented characters inside terms!!! Our
database is not suited to handle these particular characters!
On the contrary, you can use apostrophes (for example: O'Neil).
2. Fields to be filled are of 3 types:
Free-text These fields have an input box that can be filled in with text. No particular rule
should be followed except for some advices that are reported below.
Single Term Fields You can check only one term in these fields.You can recognize
these fields because they have a radio button (an empty circle in Windows
and Macintosh or an empty diamond in Unix) at the left of each predefined
choice.
Multiple Terms Fields. You can check one or more terms in these fields. You can recognize
these fields because they have a checkbox (an empty square) at the left of
each predefined choice. The possibility to fill in more than a term is useful
because heterogeneous data could be present inside a family. Suppose you
have a family where there are persons with different hearing impairment e.g.
some people present with moderate hearing impairment and others with
severe. In this case you can check both the term Moderate and the
term Severe.
B. How to Fill In the Faxable Form: Specific Fields
1. FAMILY CODE
To respect patients' privacy you should give a family a code.
This is a 13 characters field whose content MUST follow these rules:
1. The first two characters are the tag of the country where the principal investigator comes
from. Internet rules are followed (for example: IT=Italy, SE=Sweden, DE=Germany,
UK=United Kingdom, FR=France, ES=Spain, BE=Belgium, NL=The Netherlands etc...).
2. The 3rd character must be an _ (underscore)
3. Characters # 4-6 must be three characters that are an ID of the principal investigator (for
example: MMA is for Martini Alessandro)
4. The 7th character must be an _ (underscore)
5. Characters # 8-9 are OT for Otosclerosis or NS for Non Syndromic kind of impairment
6. The 10th character must be an _ (underscore)
7. Characters # 11-13 are a "three number tag" that is a progressive id for the family
discovered by an investigator. This way a maximum of 999 families for each principal
investigator is allowed. Numbers <100 must prefixed with zeros (e.g. 003, 027 etc..).
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This is an example of how a FAMILY CODE must be written: IT_MMA_OT_001
This means that this is a family with Otosclerosis (OT) filed as #1 (001)in the records of Dr.
Alessandro Martini (MMA) in Italy (IT).
2. RESEARCHER, INSTITUTION, ADDRESS
No particular rule must be followed.
3. E-MAIL
If you do not have an e-mail address, please leave this cell blank.
4. CITY, COUNTRY
No particular rule must be followed. Keep in mind that CITY field include also the ZIP code.
5. INHERITANCE, TINNITUS, TYPE, CONSANGUINEITY, RACE
These are only one term fields, i.e., they can contain only one term. You can recognize these
fields because they have a radio button (an empty circle in Windows and Macintosh, an empty
diamond in Unix) at the left of each predefined choice.
6. FREQUENCY IMPAIRMENT, HEARING LEVELS, ONSET, PROGRESSION,
LATERALISATION, VESTIBULAR ACTIVITY, Rx MALFORMATIONS
These fields can contain one or more terms. You can recognize these fields because they have
a checkbox (an empty square) at the left of each predefined choice. The possible content of
these fields is mostly explicative in itself. In the case of FREQUENCY IMPAIRMENT and
HEARING LEVELS IMPAIRMENT, a legend explaining the meaning of each term is
reported below the field it refers to.
7. GEOGRAPHIC ORIGIN
This is where the family come from. This is not a searchable field so in principle could be
narrowed down to a single village :) No particular rule must be followed.
8. PRESENTATION
This is another field that can contain only one term. The predefined terms are homogeneous
i.e. no intrafamilial differences in phenotype are present and heterogeneous which refers to
intrafamilial differences in phenotype (e.g. different frequency ranges impaired or different
levels of impairment within the family).
9. HEREDITARY TREE
Please DO NOT fill in this field!!!
We'll do it for you, if you send us an image of hereditary tree. See the instructions below.
10. AFFECTED
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Fill in the input box with the arabic number of subjects affected in the study. For otosclerotic
families type the number of the affected members under study and, within brackets, the
character + (plus) and the number of subjects with:
1. Normal hearing and absence of stapedial refexes
2. Stapedial refexes with the on-off effect
For example: 5 (+3)
11. GENERATIONS
Fill in with the arabic number of generation(s) available in the family under study.
12. GeneLOCALISATION, GeneID, CHROMOSOME, MUTATION
Specify if known, otherwise fill in the cell with Unknown.
13. PHENOTYPE
Please DO NOT fill in this field!!!
It will become an hyperlink to the phenotype database when more information about mutation
loci and phenotypes will be available.
14. NOTES
In this field you can add notes if useful to characterise the family (e.g. brief description of Rx
Malformations). You are limited at no more than 250 characters (spaces included).
C. Images of the Hereditary Tree
You can also send optionally an image of the hereditary pattern of transmission of the hearing
impairment inside a family. The name of the files MUST follow the rules of DOS filenames,
i.e. 8 characters for the filename, a dot --> '.'and an extension of 3 characters. The name of
the file is basically the same use for the Family Code, i.e.:
1. Characters # 1-3 must be three characters that are an ID of the principal investigator (for
example: MMA is for Martini Alessandro)
2. Characters # 4-5 are OT for Otosclerosis or NS for Non Syndromic kind of impairment
3. Characters # 6-8 are a "three number tag" that is a progressive id for the family
discovered by an investigator.
4. The extension (the part of the filename after the dot) should be JPG or GIF depending
on the graphics format chosen.
This is an example of how to name a hereditary tree image: MMAOT001.GIF
This means that this is the hereditary tree image of the family whose code was
IT_MMA_OT_001.
To send images you can:
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1. Send a 16 colours .GIF or .JPG image not exceeding 400 (x axis) x 300 (y axis) pixels as
an e-mail attachment to H.E.A.R. Database Administrator. Please, use the MIME or
BinHex type of encoding to send data, NOT the uuencode method!
2. Send a good quality image of the hereditary tree by mail or by fax to:
Dr. M. Mazzoli
Servizio di Audiologia
Ospedale S. Anna
Corso Giovecca 203
44100 FERRARA - ITALY
Phone: +39 (532) 29-5407
Fax: +39 (532) 29-5887
E-mail: [email protected]
-----------------------------------------------------------------------© 1997-98 H.E.A.R. - University of Ferrara - Author: Leopoldo Saggin
Mail to: [email protected] - Last Revision: January 21, 1998
Best viewed on Netscape 3.0 or higher
------------------------------------------------------------------------
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FIG. 3, 4, 5, 6, 7,
Legends to figures
FIG. 3 : Genetic hearing impairment - Family database: Index
FIG. 4 : Submission form to send data through www-interfaced e-mail.
FIG. 5 : Submission form to send data via fax.
FIG. 6 : Query form of the family database.
FIG. 7: Examples of family records obtained with a query: inheritance=dominant. Note that
the underlined field is a hyperlink to the .GIF image representing the family tree, as shown in
the inset.
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Other interesting sites...
THE "VIRTUAL" - MEDICAL CENTER
OTOLARYNGOLOGY, OTORHINOLARYNGOLOGY
& OPHTHALMOLOGY CENTER
http://www-sci.lib.uci.edu/~martindale/MedicalAudio.html
INFOBIOGEN (ie. INFormatics for BIOmolecules and GENomes), a French national centre
for Bioinformatics has been created at Villefuif on January 1995 with support from the
Ministère de l'Enseignement Supérieur et de la Recherche (French National Research Agency)
and the AFM (French Association against Muscular Distrophy)
http://www.infobiogen.fr/index-english.html
The Genome Database- an international collaboration in support to the Human Genome
Project
http://gdbwww.gdb.org/
The Boys Town Research Registry for Hereditary Hearing Loss
http://www.boystown.org/hhirr/
National Center for Biotechnology Information - Human/Mouse Homology Relationships
http://www3.ncbi.nlm.nih.gov/Homology/
Laboratories of Genetics at Rockefeller University
http://linkage.rockefeller.edu/
Linkage Designer Homepage
http://hgins.uia.ac.be/dnalab/ld.html
OMIM Home Page -- Online Mendelian Inheritance in Man
http://www3.ncbi.nlm.nih.gov/Omim/
MGD: The Mouse Genome Database
http://www.informatics.jax.org/mgd.html
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