Nonsyndromic X-linked intellectual deficiency in three brothers with a novel MED12 missense mutation [c.5922G>T (p.Glu1974His)]

Abstract

X-linked intellectual deficiency (XLID) is a large group of genetic disorders. MED12 gene causes syndromic and nonsyndromic forms of XLID. Only seven pathological mutations have been identified in this gene. Here, we report a novel mutation segregating with XLID phenotype. This mutation could be in favor of genotype-phenotype correlations.

Keywords: Intellectual deficiency; MED12; X-Inactivation; X-exome sequencing; X-linked; mutation.

Figure 1

Pedigree of the family. Black symbols indicate intellectual deficiency due to the MED12 mutation. The arrow shows the index case. Circle with a centered black dot represents symptomatic carrier female.

Figure 2

Photographs and brain MRI of patient II-3. (A, B): Facial features include long narrow face with a high forehead, frontal hair upsweep, mildly downslanting palpebral fissures, high nasal bridge, a long philtrum, and a small mouth. (C, D): Clinodactyly of the fifth finger of both hands and flat foot. (E, F): Midsagittal (E) and axial (F) brain MRI sections showing normal corpus callosum.

Figure 3

Schematic representation of MED12 cDNA. The boxes represent the 45 exons. They are numbered from 1 to 45. The position and type of all mutations involved in Intellectual Deficiency which are collected from literature are shown in the upper part. The novel mutation described in this study is shown by an asterisk (*).