Microdeletion Syndromes Detected by FISH - 73 Positive from 374 Cases

• Published in: International journal of human genetics Vol. 10; no. 1-3; pp. 15 - 20
• Main Authors: Madon, Prochi F., Athalye, Arundhati S., Sanghavi, Kunal, Parikh, Firuza R.
• Format: Journal Article
• Language: English
• Published: Routledge 01.03.2010
• Subjects: Angelman. Williams; Autism; Cytogenetics; DiGeorge; Fluorescence; Prader-Willi
• ISSN: 0972-3757; 2456-6330
• DOI: 10.1080/09723757.2010.11886080

Fluorescence in situ hybridization (FISH) has facilitated the detection of microdeletions seen in Prader-Willi/Angelman (PW/AS), Williams and DiGeorge syndromes. Out of 374 suspected cases tested at Jaslok Hospital inthe past 5 years, 73 were positive, including 29 cases of Angelman, 16 of Prader-Willi, 24 of Williams and 4 ofDiGeorge syndrome. Male preponderance was seen, mainly in Williams syndrome. The mechanisms causing Prader-Willi and Angelman syndrome include microdeletions, intragenic mutations, uniparental disomy and imprintingdefects, though FISH can only detect microdeletions. Metaphase FISH helped to detect 1 case each with deletion ofthe control (PML) signal and duplication of the critical PW/AS region, which are associated with autism. Onesuspected case of Prader-Willi syndrome had a Robertsonian translocation t(14;15)(q10;q10) which led to a deletionof a major part of the SNRPN region in 10% cells, resulting in low-grade mosaicism. Another FISH-positive case wasdue to a reciprocal translocation t(2;15)(q37;q11), where loss of critical genes at the breakpoint on chromosome 15caused the Prader-Willi phenotype. FISH in a child with an Angelman phenotype showed no microdeletion, thoughTrisomy 15 was seen in 1 metaphase suggesting uniparental disomy due to trisomy rescue. A known polymorphism inthe form of an additional tiny green signal on chromosome 14 was observed in 17 of 284 (6%) cases studied forPrader-Willi/Angelman syndrome. Another inherited polymorphism was seen in 5 cases, where one control signal wasvery small. Prenatal diagnosis was carried out with normal results, in 12 women with a previously affected child.