Identification of a novel homozygous TRAPPC9 gene mutation causing non‐syndromic intellectual disability, speech disorder, and secondary microcephaly

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2017-12, Vol.174 (8), p.839-845
• Main Authors: Abbasi, Ansar A., Blaesius, Kathrin, Hu, Hao, Latif, Zahid, Picker‐Minh, Sylvie, Khan, Muhammad N., Farooq, Sundas, Khan, Muzammil A., Kaindl, Angela M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; autosomal recessive intellectual disability; Carrier Proteins - genetics; Child; Child, Preschool; Codon, Nonsense; Exome; Female; Genetics; Homozygote; Humans; Intellectual disabilities; Intellectual Disability - complications; Intellectual Disability - genetics; Intercellular Signaling Peptides and Proteins; Magnetic resonance imaging; Male; Microcephaly; Microcephaly - complications; Microcephaly - genetics; Microencephaly; Mutation; NF‐κB signaling; Nonsense mutation; Pedigree; Point mutation; Prognosis; Speech; Speech disorders; Speech Disorders - complications; Speech Disorders - genetics; Substantia alba; Syndrome; TRAPPC9 gene; vesicle trafficking; Young Adult
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.32602

TRAPPC9 gene mutations have been linked recently to autosomal recessive mental retardation 13 (MRT13; MIM#613192) with only eight families reported world‐wide. We assessed patients from two consanguineous pedigrees of Pakistani descent with non‐syndromic intellectual disability and postnatal microcephaly through whole exome sequencing (WES) and cosegregation analysis. Here we report six further patients from two pedigrees with homozygous TRAPPC9 gene mutations, the novel nonsense mutation c.2065G>T (p.E689*) and the previously identified nonsense mutation c.1423C>T (p.R475*). We provide an overview of previously reported clinical features and highlight common symptoms and variability of MRT13. Common findings are intellectual disability and absent speech, and frequently microcephaly, motor delay and pathological findings on MRI including diminished cerebral white matter volume are present. Mutations in TRAPPC9 should be considered in non‐syndromic autosomal recessive intellectual disability with severe speech disorder.