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AbstractFluorescence in situhybridization (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.

AbstractMale partners of infertile couples are known to frequently have abnormal semen parameters. Some of these cases are due to underlying genetic factors such as Y chromosome microdeletions, an abnormal karyotype or cystic fibrosis mutations. Y chromosome microdeletions generally cannot be detected by karyotyping. At our clinic we undertook a study of male partners of infertile couples to determine the frequency and common loci of Y chromosome microdeletions in India, using the PCR technique. We studied 100 patients mainly having azoospermia (AZ) or oligoasthenoteratozoospermia (OAT). Multiplex PCR analysis for 18 loci on the Y chromosome was carried out using commercially available kit (Promega Version 1.1). Y chromosome microdeletions were observed in 12/100 (12%) patients including 8/27 (29.63%) with azoospermia, 3/56 (5.35%) with oligoasthenoteratozoospermia and 1/ 7 (14.28%) with only asthenoteratozoospermia. All loci of the DAZ gene were deleted along with DYS237 and DYS236 from AZFd in 5/27 (18.52%) azoospermic males studied. The most commonly deleted loci were DYS240 in 11/12 (91.67%) and DYS219 in 7/12 (58.33%) patients with microdeletions. The use of ICSI in such patients can lead to transmission of Y chromosome microdeletions and subsequent infertility from father to son. Hence screening for Y chromosome microdeletions will help in the proper counseling and management of couples with male factor infertility.

AbstractFanconi Anemia (FA) is a rare autosomal recessive disorder associated with pancytopenia, spontaneous chromosome instability and a variety of congenital anomalies. Hypersensitivity to bifunctional alkylating or DNA crosslinking agents like Mitomycin C (MMC), Diepoxybutane (DEB) and Nitrogen Mustard (HN2) is used as a differential diagnostic test. A variable phenotype and age of onset of anemia make diagnosis difficult in some cases. We report a case of Fanconi anemia detected by the MMC stress test in a 2 year old boy, operated for bilateral syndactyly and contractures of fingers. He had a bifid thumb on the left hand and bilateral triphalangeal thumbs. There was no history of consanguinity or malformations, though a maternal uncle had a bifid thumb. USG in a subsequent pregnancy showed bony anomalies like scoliosis, talipes, contractures and radial aplasia, consistent with FA. The parents opted for termination. An early diagnosis of FA in a non-manifesting child would provide more time to explore different treatment options, since a delay in diagnosis could have serious consequences.

To assess sperm characteristics and fertility before and after varicocelectomy using computer-assisted semen analysis (CASA).