Mochida et al. (2009) reported a consanguineous Israeli Arab pedigree in which 3 girls had moderate to severe mental retardation and postnatal microcephaly. One girl, at age 7 years 10 months, had severe cognitive delay and could speak ... Mochida et al. (2009) reported a consanguineous Israeli Arab pedigree in which 3 girls had moderate to severe mental retardation and postnatal microcephaly. One girl, at age 7 years 10 months, had severe cognitive delay and could speak only a few words. She had normal motor development and could walk, but showed bruxism and hand-flapping movements. Brain MRI scans at age 2 and 4 years showed a thin corpus callosum and reduced volume of the cerebral white matter. Brain MRI of her 4-year-old affected sister also showed a thin but fully formed corpus callosum, decreased volume of the cerebral white matter, and hypoplasia of the inferior cerebellar vermis. Brain MRI was not reported for the third child. None of the patients had dysmorphic features, autistic features, or seizures, and there was no evidence of developmental regression. Philippe et al. (2009) reported 3 brothers, born of consanguineous Tunisian parents, with autosomal recessive mental retardation associated with mild microcephaly, myelination defect, and truncal obesity in the first year of life. One child, first examined at age 10 years, had severe mental retardation with significant speech delay and a friendly personality. He had mild microcephaly, truncal obesity, hypertelorism, short neck, and prominent upper central incisors. Examination at age 19 showed progressive microcephaly and short, smooth philtrum, and brain MRI showed unusual white matter abnormalities. The second child had unilateral cleft lip, delayed speech, hypotelorism, short neck, prominent upper central incisors, short, smooth philtrum, and long, thin fingers. He understood simple commands and had a happy disposition and hyperactivity. The third affected child had global developmental delay, but was less severely affected. At age 4, he could communicate verbally with a few words and understood commands, and was able to performed simple tasks. He also had hyperactive behavior. Mir et al. (2009) reported a consanguineous Pakistani family with MRT13. There was either microcephaly or borderline microcephaly. Three affected individuals were studied in detail. A 3-year-old girl did not walk independently and spoke fewer than 20 meaningful words. She could not feed herself and had not achieved continence. A 6-year-old girl started walking at 4 years of age, was overweight, could not use full sentences, and had clonic/tonic seizures. A 9-year-old boy started walking at 5 years of age and could communicate basic needs. There were no autistic features or dysmorphic features. Abou Jamra et al. (2011) reported a large consanguineous Syrian family with MRT13. The patients had neonatal hypotonia, severe motor delay with walking between ages 5 and 7 years, single words or no speech, growth retardation, stereotypic movements, and hand flapping. They also shared some dysmorphic features, including low frontal hairline, synophrys, and microcephaly. One patient had seizures. Genetic analysis revealed a homozygous truncating mutation in the TRAPPC9 gene (611966.0001). Marangi et al. (2013) reported 2 sisters, born of unrelated parents from southern Italy, with MRT13. Both had hypotonia at birth and showed delayed psychomotor development; 1 child never learned to stand up or utter single words. Both had a small head and a distinctive craniofacial appearance with brachycephaly, round face, hypertelorism, straight eyebrows, synophrys, wide nasal bridge, fleshy ears, and downturned mouth. One girl had recurrent febrile seizures. Both had abnormal brain MRI findings, including decreased cerebral white matter volume, sulcal enlargement, thinning of the corpus callosum, and reduced cerebellar volume. There were also several areas of T2 hyperintensity in the subcortical white matter. Both girls were obese and severely mentally disabled. One showed a friendly disposition. In a review of the literature, Marangi et al. (2013) concluded that the phenotype associated with loss-of-function mutations in the TRAPPC9 gene is recognizable and can be characterized by dysmorphic facial appearance, obesity, hypotonia, moderate to severe intellectual disability, and consistent brain abnormalities.
By genomewide linkage analysis followed by candidate gene sequencing of an Israeli Arab family with nonsyndromic mental retardation. Mochida et al. (2009) identified a homozygous truncating mutation in the TRAPPC9 gene (R475X; 611966.0001) on chromosome 8q24. Mir et ... By genomewide linkage analysis followed by candidate gene sequencing of an Israeli Arab family with nonsyndromic mental retardation. Mochida et al. (2009) identified a homozygous truncating mutation in the TRAPPC9 gene (R475X; 611966.0001) on chromosome 8q24. Mir et al. (2009) identified an R475X mutation in affected members of a Pakistani family with MRT13. Philippe et al. (2009) identified a nonsense mutation in the TRAPPC9 gene (611966.0002) in 3 Tunisian brothers with autosomal recessive mental retardation. Mir et al. (2009) identified a deletion in the TRAPPC9 gene (611966.0003) in affected members of an Iranian family (family M001) reported by Najmabadi et al. (2007) as showing linkage to chromosome 8q24. Affected members had severe nonsyndromic mental retardation, were ambulatory but nonverbal, and had microcephaly. There were no seizures or dysmorphic features. In 2 sisters, born of unrelated parents from southern Italy, with MRT13, Marangi et al. (2013) identified a homozygous truncating mutation in the TRAPPC9 gene (611966.0004).