Whole-exome analysis of foetal autopsy tissue reveals a frameshift mutation in OBSL1, consistent with a diagnosis of 3-M Syndrome. (December 2015)

• Record Type: Journal Article
• Authors: Marshall, Christian; Farrell, Sandra; Cushing, Donna; Paton, Tara; Stockley, Tracy; Stavropoulos, Dimitri; Ray, Peter; Szego, Michael; Lau, Lynette; Pereira, Sergio; Cohn, Ronald; Wintle, Richard; Abuzenadah, Adel; Abu-Elmagd, Muhammad; Scherer, Stephen
• Is Part Of: BMC genomics. Volume 16:Number 1(2015)
• Page Start: 1
• Page End: 7
• Publication Date: 2015-12
• Subjects: exome sequencing -- frameshift mutation -- OBSL1 -- skeletal dysplasia -- 3-M Syndrome; Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/1471-2164-16-S1-S12
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Background We report a consanguineous couple that has experienced three consecutive pregnancy losses following the foetal ultrasound finding of short limbs. Post-termination examination revealed no skeletal dysplasia, but some subtle proximal limb shortening in two foetuses, and a spectrum of mildly dysmorphic features. Karyotype was normal in all three foetuses (46, XX) and comparative genomic hybridization microarray analysis detected no pathogenic copy number variants. Results Whole-exome sequencing and genome-wide homozygosity mapping revealed a previously reported frameshift mutation in theOBSL1 gene (c.1273insA p.T425nfsX40), consistent with a diagnosis of 3-M Syndrome 2 (OMIM #612921), which had not been anticipated from the clinical findings. Conclusions Our study provides novel insight into the early clinical manifestations of this form of 3-M syndrome, and demonstrates the utility of whole exome sequencing as a tool for prenatal diagnosis in particular when there is a family history suggestive of a recurrent set of clinical symptoms.