Mental Retardation, Autosomal Dominant 30

A number sign (#) is used with this entry because autosomal dominant mental retardation-30 (MRD30) is caused by heterozygous mutation in the ZMYND11 gene (608668) on chromosome 10p15.

Clinical Features

Coe et al. (2014) identified 7 individuals from 6 families with loss-of-function variants in the ZMYND11 gene. In the 1 familial case, the son had global developmental delay, speech delay, social difficulties, behavioral problems, and dysmorphic facial features; the more mildly affected father had developmental delay and behavioral problems including aggressive behavior in childhood with mood swings. Patients with mutations in ZMYND11 showed mild intellectual disability and subtle facial dysmorphisms, including hypertelorism, ptosis, and a wide mouth. Both females studied were described as having autistic tendencies, while 3 of 4 males had aggression.

Molecular Genetics

Coe et al. (2014) created an expanded copy number variant (CNV) morbidity map from 29,085 children with developmental delay in comparison to 19,584 healthy controls, identifying 70 significant CNVs. They then resequenced 26 candidate genes in 4,716 additional cases with developmental delay or autism and 2,193 controls. An integrated analysis of CNV and single-nucleotide variant (SNV) data pinpointed 10 genes enriched for putative loss of function. Among these was ZMYND11, in which Coe et al. (2014) identified 6 truncating mutations (e.g., 608668.0001-608668.0005) in 7 individuals with MRD30 from 6 families. One affected individual had inherited the mutation from his more mildly affected father. In 2 cases, those of a 9-year-old female and a 17-year-old female, the mutations occurred as de novo events. In the remaining patients, inheritance could not be determined.