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 the OBSL1 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.
Original language | English (US) |
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Article number | S12 |
Journal | BMC genomics |
Volume | 16 |
Issue number | 1 |
DOIs | |
State | Published - Jan 15 2015 |
Keywords
- 3-M Syndrome
- Exome sequencing
- Frameshift mutation
- OBSL1
- Skeletal dysplasia
ASJC Scopus subject areas
- Biotechnology
- Genetics