Single suture craniosynostosis: Identification of rare variants in genes associated with syndromic forms.
Christine M ClarkeVincent T FokJennifer A GustafsonMatthew D SmythAndrew E TimmsChris D FrazarJoshua D SmithCraig B BirgfeldAmy LeeRichard G EllenbogenJoseph S GrussRichard A HopperMichael L CunninghamPublished in: American journal of medical genetics. Part A (2017)
We report RNA-Sequencing results on a cohort of patients with single suture craniosynostosis and demonstrate significant enrichment of heterozygous, rare, and damaging variants among key craniosynostosis-related genes. Genetic burden analysis identified a significant increase in damaging variants in ATR, EFNA4, ERF, MEGF8, SCARF2, and TGFBR2. Of 391 participants, 15% were found to have damaging and potentially causal variants in 29 genes. We observed transmission in 96% of the affected individuals, and thus penetrance, epigenetics, and oligogenic factors need to be considered when recommending genetic testing in patients with nonsyndromic craniosynostosis.