Trappc9 Case Study

Mutations in TRAPPC9 have been identified in patients with Non-Syndromic Autosomal Recessive Mental Retardation (NS-ARMR). These mutations were characterized in separate families of Middle Eastern Arab descent. One separate case involves three consanguineous Israeli Arab girls carried a TRAPP9 truncation (c.1422C>T)156. The second case was identified in a large consanguineous Pakistani family193, patients were characterized with a nonsense mutation R475X in exon 7. Another mutation that resulted in a frameshift and premature truncation causing p.Leu772TrpfsX7 was caused by a homozygous 4bp deletion: c.2311-2314 delTGTT has been identified in Iranian family166. A homozygous nonsense mutation resulting in p.Arg570-to-ter (R570X) due to c.1708C>T transcription has been identified in three Tunisian brothers from a consanguineous …show more content…
All NS-ARMR patients show similar mental retardation clinical phenotypes ranging from moderate to severe. Clinical phenotypes associated with NS-ARMR include but not limited to moderate to severe MR, and variable postnatal microcephaly. Mild facial dysmorphism and truncal obesity was reported for Tunisian brothers otherwise no facial dysmorphism was reported in Pakistani, nor the Israeli Arab nor the Iranian patients. Phenotypes associated with TRAPPC9 mutations are consistently associated with postnatal microcephaly, speech delay and neuroradiologial abnormality of the cerebral white matter, corpus callosum and cerebellum99, peculiar facial appearance, obesity, hypotonia143. MRI findings show diminished cerebral white matter volume, with sulcal enlargement, thinning of corpus callosum and mild cerebellar volume loss. The phenotypes have been linked to the down-regulation of the NF-kB activation but it is possible that the trafficking aspect of TRAPPC9 may also be