Mental Retardation, X-Linked 101

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-101 (MRX101) is caused by mutation in the MID2 gene (300204) on chromosome Xq22. One such family has been reported.

Clinical Features

Geetha et al. (2014) reported a large family from northern India in which 11 males spanning 3 generations had mental retardation. All 6 patients evaluated had global developmental delay. Facial dysmorphism was not prominent, but several patients had long face, prominent ears, and squint or strabismus. Two had seizures. Most also had hyperactivity, often with aggressive outbursts.

Inheritance

The transmission pattern in the family with MRX101 reported by Geetha et al. (2014) was consistent with X-linked recessive inheritance.

Molecular Genetics

In affected members of a family with MRX101, Geetha et al. (2014) identified a hemizygous missense mutation in the MID2 gene (R347Q; 300204.0001). The mutation was found using a combination of linkage analysis and targeted next-generation sequencing. Carrier females in the family were unaffected. Transfection of the mutation in HEK293T cells showed abnormal localization of the mutant protein, which was found in aggregate form or enclosed in vesicles in the cytoplasm rather than being bound to microtubules. By direct sequencing of the coding exons of the MID2 gene among 480 patients with intellectual disability, Geetha et al. (2014) identified an individual with a missense mutation (N343S); however, functional assays indicated that this mutation may not be disease causing.