Cytogenetic microarray in structurally normal and abnormal foetuses: a five year experience elucidating in creasing acceptance and clinical utility

The aim of the present study was to evaluate the diagnostic yield of prenatal cytogeneticmicroarray (CMA) in structurally normal and abnormal foetuses and record the acceptance rate of CMA for prenatal diagnosis over a course of five year. In 128 structurally normal and abnormal foetuses, CMA was performed along with foetal karyotype, after exclusion of aneuploidy by quantitative fluorescence polymerase chain reaction. The microarray was able to detect the pathogenic variants in 5.5% cases; the diagnostic yield in structurally abnormal foetuses was 8.8% and 4.7% in foetuses with a high aneuploidy risk. Balanced and unbalanced translocations, and low level mosaicism were detected. Reanalysis of variants of uncertain significance identified pathogenic variant. The study shows higher diagnostic yield in structurally abnormal cases, the importance of foetal karyotype and reanalysis in microarray. The acceptance rate of prenatal CMA increased five-fold over a period of five year

Molecular Testing of MECP2 Gene in Rett Syndrome Phenotypes in Indian Girls

Objective: To assess yield of MECP2 gene sequence variationsanalysis and large deletions in suspected cases of Rettsyndrome.Design: Descriptive study.Setting: Tertiary-care medical genetics center.Patients: Girls with neuroregression, postnatal microcephaly andsigns and symptoms suggestive of classical and atypical Rettsyndrome were classified into two groups. Group I consisted ofgirls with Classical and atypical Rett syndrome on basis on theRevised Rett Syndrome diagnostic criteria, 2010. Group II includedgirls with neuroregression and postnatal microcephaly and otherRett like features but not fulfilling the above criteria.Procedure: Sanger sequencing of coding regions and largedeletional analysis of MECP2 gene.Outcome measure: Identification of mutation in MECP2 gene.Result: Mutation in MECP2 gene was identified in 74% (14/19) ingroup I and none (0/17) in group II. The mutation detection ratewas 93% (13/14) in group I classical Rett syndrome girls (2 withlarge deletions identified with Multiplex ligation dependent probeamplification) and 20% (1/5) in group I atypical Rett syndromegirls. One novel MECP2 sequence variation was identified ingroup I classical Rett syndrome.Conclusion: The yield of the mutation detection in MECP2 ishigher in classical Rett syndrome. In girls with some Rett likefeatures, but not fulfilling revised Rett syndrome diagnosticcriteria, mutation testing for MECP2 gene has a low yield