Mental Retardation, Autosomal Recessive 47

A number sign (#) is used with this entry because of evidence that autosomal recessive mental retardation-47 (MRT47) is caused by homozygous mutation in the FMN2 gene (606373) on chromosome 1q43.

Clinical Features

Law et al. (2014) reported 5 patients from 2 unrelated consanguineous families with nonsyndromic mental retardation. All patients showed delayed development, with cognition and speech more affected than motor skills. Two patients had hypotonia. Speech was limited to a few words in most patients. Two patients had controlled complex partial seizures. At 14 to 30 years of age, all except 1 were dependent for activities of daily living. Brain imaging in 2 patients was normal; there were no additional neurologic or dysmorphic features.

Inheritance

The transmission pattern of MRT47 in the families reported by Law et al. (2014) was consistent with autosomal recessive inheritance.

Molecular Genetics

In affected members of 2 unrelated consanguineous families with autosomal recessive mental retardation, Law et al. (2014) identified 2 different truncating mutations in the FMN2 gene (606373.0001 and 606373.0002). The mutations were found by a combination of linkage analysis and whole-exome sequencing. Fibroblasts that were derived from 1 patient, an unaffected family member, and a control were reprogrammed to form neural cells and showed no differences in survival, differentiation, dendritic complexity, or nuclear morphology; however, patient-derived cells showed a 43% reduction in synaptic density compared to the other 2 cell lines. Law et al. (2014) suggested that FMN2 may be required for regulation of the actin cytoskeleton during dendritic spine development, maturation, or remodeling, and that loss of FMN2 function may contribute to intellectual disability due to decreased synaptic density.