Van Maldergem et al. (2013) reported 9 affected males from 4 unrelated families with nonsyndromic X-linked mental retardation. One of the families with 2 affected individuals had previously been reported by Cantagrel et al. (2004). The patients had ... Van Maldergem et al. (2013) reported 9 affected males from 4 unrelated families with nonsyndromic X-linked mental retardation. One of the families with 2 affected individuals had previously been reported by Cantagrel et al. (2004). The patients had delayed psychomotor development, absent or poor speech development, and postnatal growth retardation, often with microcephaly. Some patients showed autistic behavioral features, such as stereotypic hand movements and repetitive behaviors. All of the patients had strabismus. Additional, more variable features included spasticity, axial hypotonia, seizures, drooling, gastroesophageal reflux, and lack of sphincter control. Some patients had dysmorphic features, including round face, short nose, short philtrum, and esotropia, although a specific pattern was not present. Female carriers were unaffected.
In affected males from 3 unrelated families with X-linked mental retardation, Van Maldergem et al. (2013) identified 3 mutations in the KIAA2022 gene. Two of the mutations resulted in premature termination and loss of function (300524.0001 and 300524.0003), ... In affected males from 3 unrelated families with X-linked mental retardation, Van Maldergem et al. (2013) identified 3 mutations in the KIAA2022 gene. Two of the mutations resulted in premature termination and loss of function (300524.0001 and 300524.0003), and the third was a duplication involving exon 1 (300524.0002) that resulted in a 60% decrease in KIAA2022 expression. The mutations were found by X-chromosome exome sequencing or microarray CGH analysis and segregated with the phenotype in the families. Carrier females were unaffected. Knockdown of KIAA2022 in cultured rat hippocampal neurons resulted in marked impairment in neurite outgrowth, including both the dendrites and the axons, suggesting a major role for KIAA2022 in neuron development and brain function. The findings indicated that loss of KIAA2022 function can cause intellectual disability with autistic features.