Mental Retardation, X-Linked 72

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-72 (MRX72) is caused by hemizygous mutation in the RAB39B gene (300774) on chromosome Xq28.

Mutation in the RAB39B gene can also cause X-linked recessive mental retardation with early-onset Parkinson disease, known as Waisman syndrome (WSMN; 311510).

Clinical Features

Russo et al. (2000) reported a 3-generation Sardinian family segregating X-linked mental retardation. Three affected individuals had seizures and 1 had features of autism (see 209850).

Giannandrea et al. (2010) reported a large family with X-linked mental retardation spanning 2 generations. There were 6 affected males, all with macrocephaly. One had obesity and 2 had features of autism.

Inheritance

The transmission pattern of mental retardation in the family reported by Russo et al. (2000) was consistent with X-linked recessive inheritance.

Mapping

In a 4-generation Sardinian family, Russo et al. (2000) observed 8 males with nonspecific X-linked mental retardation and 6 carrier females. Two-point linkage analysis demonstrated linkage to markers in Xq28; maximum lod score = 2.71 at theta = 0.00. The authors excluded involvement of the GDI1 gene (300104), which maps to the same region and is mutated in other families with nonspecific mental retardation (MRX41; 300849).

Molecular Genetics

In 2 unrelated families with X-linked mental retardation, including the family reported by Russo et al. (2000), Giannandrea et al. (2010) identified different hemizygous loss-of-function mutations in the RAB39B gene (300774.0001-300774.0002) that segregated with the disorder.