Genotype-phenotype evaluation of MED13L defects in the light of a novel truncating and a recurrent missense mutation.

Genotype-phenotype evaluation of MED13L defects in the light of a novel truncating and a recurrent missense mutation. Eur J Med Genet. 2017 Jun 20;: Authors: Asadollahi R, Zweier M, Gogoll L, Schiffmann R, Sticht H, Steindl K, Rauch A Abstract A decade after the designation of MED13L as a gene and its link to intellectual disability (ID) and dextro-looped transposition of great arteries in 2003, we previously described a recognizable syndrome due to MED13L haploinsufficiency. Subsequent reports of 22 further patients diagnosed by genome-wide testing further delineated the syndrome with expansion of the phenotypic spectrum and showed reduced penetrance for congenital heart defects. We now report two novel patients identified by whole exome sequencing, one with a de novo MED13L truncating mutation and the other with a de novo missense mutation. The first patient indicates some facial resemblance to Kleefstra syndrome as a novel differential diagnosis, and the second patient shows, for the first time, recurrence of a MED13L missense mutation (p.(Asp860Gly)). Notably, our in silico modelling predicted this missense mutation to decrease the stability of an alpha-helix and thereby affecting the MED13L secondary structure, while the majority of published missense mutations remain variants of uncertain significance. Review of the reported patients with MED13L haploinsufficiency indicates moderate to severe ID and facial anomalies in all pati...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research