Download Oculocutaneous albinism type 1A

Oculocutaneous albinism
type 1A
Adrienne Bonvini
What is it?
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It is an autosomal recessive disorder
characterized by an absence of pigment
in the eyes, hair, and skin.
This specific type is characterized by
complete lack of tyrosinase activity
because an inactive form of the enzyme
is produced.
Occurs at a rate of 1/40,000 people
Clinical Features
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Reduced synthesis
of melanin in the
skin, hair, and eyes.
Translucent irises
Vision usually in the
range of 20/100 to
20/400
Molecular Genetics
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OCA1A is caused by mutations of the TYR gene that
produce a inactive form of the tyrosinase enzyme.
Parents of an affected child are considered to be
obligate heterozygotes, each carrying a single copy of
the disease-causing mutation in the TYR gene.
The gene is located on chromosome 11, at 11q14 –
q21
The lack of this enzyme blocks the first step of the
melanin biosynthetic pathway, and no melanin is
formed in the appropriate melanocytes.
Molecular genetic testing
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There is evidence of undetected
mutations that may be responsible for
OCA1. This evidence is from people
with the OCA1A pheotype with only a
single identifiable mutation, who are
most likely compound heterozygotes
with a second mutation that has yet to
be identified.
Mutations of the TYR gene
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Missense subsitutions in the tyrosinase gene alters
codons 355 (thr to lys) and codon 365 (asp to asn).
These mutations cause the tyrosinase activity to be
disrupted, causing the lack of pigmentation seen in
albinism. Both of these mutations occur in the
copper binding region of the enzyme.
Visualization of mutations
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thr to lys
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asp to asn
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An example of a tyrosinase
Bibliography
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http://www.rcsb.org/pdb/explore/explore.do?
structureId=1WX2
http://www.ncbi.nlm.nih.gov/entrez/dispomi
m.cgi?id=606933&a=606933_AllelicVariant00
03
http://www.ncbi.nlm.nih.gov/entrez/query.fcg
i?db=gene&cmd=Retrieve&dopt=full_report&
list_uids=7299
http://www.ncbi.nlm.nih.gov/entrez/dispomi
m.cgi?id=203100