Mental Retardation, Autosomal Recessive 58

A number sign (#) is used with this entry because of evidence that autosomal recessive mental retardation-58 (MRT58) is caused by homozygous or compound heterozygous mutation in the ELP2 gene (616054) on chromosome 18q12.

Clinical Features

Najmabadi et al. (2011) reported 2 unrelated consanguineous families in which 3 members of each family had nonsyndromic mental retardation. Clinical details were not provided, but 1 family (8500061) was reported to have mild and the other (G017) to have severe intellectual disability.

Cohen et al. (2015) reported 2 adult brothers with MRT58. They showed global developmental delay since infancy and had poor head control. One lost the ability to walk at age 9 due to progressive spasticity and had no meaningful language, and the other never walked or talked. Both patients had behavioral problems, including aggressiveness, impulsivity, and self-injury. Neurologic examination showed truncal hypotonia, lower limb spasticity with hyperreflexia, choreoathetosis, and stereotypical movements. One patient had short stature. Brain MRI was normal.

Inheritance

The transmission pattern of MRT58 in the family reported by Cohen et al. (2015) was consistent with autosomal recessive inheritance.

Molecular Genetics

Najmabadi et al. (2011) performed homozygosity mapping followed by exon enrichment and next-generation sequencing in 136 consanguineous families (over 90% Iranian and less than 10% Turkish or Arabic) segregating syndromic or nonsyndromic forms of autosomal recessive intellectual disability. In 2 families (families G017 and 8500061) in which affected individuals had nonsyndromic mental retardation, Najmabadi et al. (2011) identified homozygous missense mutations in the ELP2 gene (T555P, 616054.0001 and R462L, 616054.0002). Functional studies of the variants and studies of patient cells were not performed.

In 2 brothers with MRT58, Cohen et al. (2015) identified compound heterozygous missense mutations in the ELP2 gene (R527W, 616054.0003 and H271R, 616054.0004). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed. However, Cohen et al. (2015) noted that the R527W mutation occurred at the same residue as the mutation reported by Najmabadi et al. (2011) as R462L (616054.0002).