A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly.

This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n=85 anencephaly and n=5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N=509), we identified 397 rare variants (MAF<1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly.
PMID: 29205322 [PubMed - as supplied by publisher]

Source: Clinical Genetics - December 4, 2017 Category: Genetics & Stem Cells Authors: Ishida M, Cullup T, Boustred C, James C, Docker J, English C, GOSgene, Lench N, Copp AJ, Moore GE, Greene NDE, Stanier P Tags: Clin Genet Source Type: research