Mental Retardation, Autosomal Recessive 57

A number sign (#) is used with this entry because of evidence that autosomal recessive mental retardation-57 (MRT57) is caused by homozygous mutation in the MBOAT7 gene (606048) on chromosome 19q13.

Clinical Features

Johansen et al. (2016) reported 16 patients from 6 unrelated consanguineous families of Middle Eastern descent with moderate to severe intellectual disability. The patients had delayed psychomotor development with poor or absent speech. Thirteen started to walk between 2 and 7 years, whereas 3 never achieved walking. Ten patients developed seizures, including 6 with infantile-onset focal, multifocal, or myoclonic epilepsy, 2 with onset of seizures at 1.5 or 2 years of age, and 2 with febrile seizures. The seizures were generally well-controlled and even remitted later in childhood in most patients. Additional features included truncal hypotonia and appendicular hypertonia. Three patients had a small head circumference, and brain imaging in 2 patients showed cortical atrophy and mild polymicrogyria, but brain imaging was normal in at least 4 other patients. Seven patients had autism spectrum disorder.

Inheritance

The transmission pattern of MRT57 in the family reported by Johansen et al. (2016) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 16 patients from 6 different consanguineous families of Middle Eastern descent with MRT57, Johansen et al. (2016) identified 5 different homozygous mutations in the MBOAT7 gene (606048.0001-606048.0005). The mutations resulted in truncated proteins, abnormal splicing, or intragenic deletions affecting critical domains. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Functional studies of the variants and studies of patient cells were not performed.

Animal Model

Lee et al. (2012) found that Mboat7-null mice were significantly smaller than controls and showed reduced postnatal survival. Histologic analysis of embryonic mutant mouse brains showed a smaller cerebral cortex and hippocampus, abnormal cortical lamination, delayed neuronal migration, gyral abnormalities, and increased number of apoptotic cells in the cortex.