* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Beckwith-Wiedemann and Russel
Genetic engineering wikipedia , lookup
Non-coding DNA wikipedia , lookup
Genome evolution wikipedia , lookup
Skewed X-inactivation wikipedia , lookup
Public health genomics wikipedia , lookup
Epigenetic clock wikipedia , lookup
Long non-coding RNA wikipedia , lookup
Y chromosome wikipedia , lookup
Epigenetics of neurodegenerative diseases wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Genealogical DNA test wikipedia , lookup
Medical genetics wikipedia , lookup
Genetic testing wikipedia , lookup
DNA paternity testing wikipedia , lookup
Oncogenomics wikipedia , lookup
Cell-free fetal DNA wikipedia , lookup
History of genetic engineering wikipedia , lookup
Epigenetics wikipedia , lookup
Neocentromere wikipedia , lookup
Gene expression profiling wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Designer baby wikipedia , lookup
Epigenetics of depression wikipedia , lookup
Behavioral epigenetics wikipedia , lookup
Gene expression programming wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
DiGeorge syndrome wikipedia , lookup
Down syndrome wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Microevolution wikipedia , lookup
Cancer epigenetics wikipedia , lookup
X-inactivation wikipedia , lookup
Genome (book) wikipedia , lookup
DNA methylation wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Epigenomics wikipedia , lookup
Epigenetics in stem-cell differentiation wikipedia , lookup
Epigenetics in learning and memory wikipedia , lookup
Genomic imprinting wikipedia , lookup
Epigenetics of diabetes Type 2 wikipedia , lookup
Beckwith-Wiedemann and Russel-Silver Syndromes About Emory Genetics Laboratory (EGL) EGL is an academic, not-for-profit organization and a global leader in genetic testing. Associated with the prestigious Emory University School of Medicine, EGL has fully integrated biochemical, cytogenetics, and molecular laboratories, employing the latest technologies for one of the most comprehensive genetic test menus available. Equally important to improving patient care through quality genetic testing is the contribution EGL makes back to the scientific and medical communities. EGL is one of only a few clinical diagnostic laboratories to openly share data with the NCBI freely available public database ClinVar (>7000 variants on >500 genes) and is also the only laboratory with a free online database (EmVClass), featuring a variant classification search and report request interface, which facilitates rapid interactive curation and reporting of variants. Beckwith-Wiedemann Syndrome Beckwith-Wiedemann syndrome (BWS) is characterized by overgrowth, congenital malformations, and increased risk for embryonic tumors. Clinical features include: • Macrosomia • Macroglosia • Omphalocele • Visceromegaly • Neonatal hypoglycemia • Embryonic tumors (Wilms tumor, hepatoblastoma, • Ear creases/pits • Hemihyperplasia neuroblastoma) Approximately 70% of BWS cases are found to have alterations in DNA methylation at two distinct, differentially methylated regions (DMRs) at 11p15. Segmental paternal uniparental disomy of chromosome 11p15.5 occurs in ~10-20% of BSW cases. DMR1 is located within the telomeric domain (also known as ICR1) and controls the expression of two genes: IGF2 and H19. Hypermethylation of DMR1 occurs in ~2-7% of BWS cases. DMR2 is located within the centromeric domain (also known as ICR2) and controls the expression of Lit1, CDKN1C, and several other genes in the region. Alterations in DNA methylation at either of the DMRs causes aberrant expression of these imprinted genes, leading to BWS. Hypomethylation of DMR2 occurs in ~50% of BWS cases. Testing Methodology EGL uses methylation-specific MLPA (MS-MLPA) to test for hypomethylation of DMR2 and hypermethylation of DMR1, indicative of BWS. One advantage of MS-MLPA is that in addition to detecting DNA methylation abnormalities (epimutations), similar to Southern blot and quantitative methylation sensitive PCR, it also detects copy number variations (CNVs; deletions and duplications) of the 11p15 region, which are estimated to be present in ~10% of patients with BWS. The presence of a CNV can increase the recurrence risk up to 50%, from that of the general population. 2165 North Decatur Road Atlanta, Georgia 30033 www.geneticslab.emory.edu Phone: 404-778-8499 Toll Free: 855-831-7447 Fax: 404-778-8559 Beckwith-Wiedemann and Russel-Silver Syndromes Russell-Silver Syndrome Russell-Silver syndrome (RSS) is characterized by intrauterine growth restriction (IUGR) and subsequent postnatal growth deficiency. Other clinical features include: • Proportionate short stature • Limb and/or facial asymmetry • Triangular faces with prominent • Normal head circumference • 5th finger clinodactyly forehead and narrow chin RSS is a genetically heterogeneous condition, associated with gene expression defects on chromosome 7 and 11. At 11p15, there is a differentially methylated region (DMR1) which controls the expression of two genes: IGF2 and H19. Hypomethylation at DMR1 on the paternal chromosome 11 leads to decreased expression of IGF2 and causes RSS in 20-35% of clinically diagnosed cases. In an additional 10% of clinically diagnosed RSS cases, maternal uniparental disomy of chromosome 7 (matUPD7) is also identified, and is believed to result in alterations of imprinted gene expression on chromosome 7; however, a single causative gene for RSS has not been identified. Testing Methodology EGL uses methylation-specific MLPA (MS-MLPA) to test for hypomethylation of DMR1 at 11p15. One advantage of MS-MLPA is that it not only detects DNA methylation abnormalities (epimutations), similar to Southern blot and quantitative methylation sensitive PCR, but it will also detect copy number variations (CNVs; deletions and duplications) of the 11p15 region. The presence of a CNV can increase the recurrence risk up to 50%, from that of the general population. To test for matUPD7, EGL uses methylation-specific PCR (MS-PCR), which targets two differentially methylated regions on chromosome 7 to detect both methylated (maternal) and unmethylated (paternal) alleles. Parental samples are not required for matUPD7 testing. EGL offers a RSS panel, which includes H19 methylation and matUPD7 analysis; both may be ordered individually. Test Code Test Name CPT ® Code(s) BW Beckwith-Wiedemann Syndrome Panel: H19 and Lit1 Methylation 81401 (x1) ZP Beckwith-Wiedemann Syndrome: H19 Methylation 81401 (x1) BL Beckwith-Wiedemann Syndrome: Lit1 Methylation 81401 (x1) NZ Russell-Silver Syndrome Panel: H19 Methylation and UPD7 81401 (x1), 81402 (x1) RT Russell-Silver Syndrome: H19 Methylation 81401 (x1) NM Russell-Silver Syndrome: UPD7 81402 (x1) **CPT® is a registered trademark of the American Medical Association. To learn more about expert EGL Laboratory Directors and Laboratory Genetic Counselors, the more than 900 tests offered at EGL, or for other questions, please visit www.geneticslab.emory.edu, call 404-778-8499, or email [email protected]. 2165 North Decatur Road Atlanta, Georgia 30033 www.geneticslab.emory.edu Phone: 404-778-8499 Toll Free: 855-831-7447 Fax: 404-778-8559