Tarpey et al. (2007) reported 4 unrelated families with X-linked mental retardation. Although the phenotype was variable, common features included mild to severe mental retardation, autistic features, slender build, poor musculature, long, thin face, high-arched palate, high nasal ... Tarpey et al. (2007) reported 4 unrelated families with X-linked mental retardation. Although the phenotype was variable, common features included mild to severe mental retardation, autistic features, slender build, poor musculature, long, thin face, high-arched palate, high nasal bridge, and pectus deformities. Two families had been diagnosed as having Lujan-Fryns syndrome (309520) and 1 as having Opitz-Kaveggia syndrome (OKS; 305450). One of the families had been reported by Graham et al. (1998). Xu et al. (2013) reported a large Chinese family in which 3 living males and 1 deceased male had nonsyndromic mild mental retardation. None of the affected individuals was known to have additional physical abnormalities. Carrier females were unaffected.
In affected members of 4 unrelated families with X-linked syndromic mental retardation, Tarpey et al. (2007) identified hemizygous mutations in the UPF3B gene (300298.0001-300298.0004).
Tarpey et al. (2009) sequenced the coding exons of the X chromosome ... In affected members of 4 unrelated families with X-linked syndromic mental retardation, Tarpey et al. (2007) identified hemizygous mutations in the UPF3B gene (300298.0001-300298.0004). Tarpey et al. (2009) sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation. They identified 3 separate nonrecurring truncating mutations in UPF3B that segregated absolutely with the phenotype. In addition to the X-linked mental retardation, affected family members had elements of the Opitz-Kaveggia and Lujan-Fryns syndromes. By exome sequencing of a Chinese family with nonsyndromic X-linked mental retardation, Xu et al. (2013) identified a hemizygous mutation in the UPF3B gene (R430X; 300298.0003). X-chromosome inactivation studies in 3 carrier mothers showed that only 18%, 17%, and 13% of lymphocytes, respectively, expressed the mutant allele. PCR analysis of patient cells showed decreased levels of mutant mRNA in the patients, suggesting that it undergoes nonsense-mediated mRNA decay. Patient cells showed higher expression of the GADD45B gene (604948), a component of the classical nonsense-mediated decay pathway compared to controls, suggesting that the UPF3B mutation caused dysregulation of this pathway.