Intellectual disability (ID) is a prevalent and genetically and clinically heterogeneous neurodevelopmental disorder. ID may be a sole phenotype of the condition (nonsyndromic ID) or it may present in conjunction with other clinical manifestations (syndromic ID). TRAPPC9 is one of several genes found to be involved in both types of ID and autism. Using whole-exome sequencing, we investigated the genetic basis of syndromic ID in a brother and sister from a consanguineous Egyptian family and detected a homozygous transition (c.2635C > T) in exon 16 of the TRAPPC9 gene. For the most part, this novel variant likely results in nonsense-mediated mRNA decay, while the residual mRNA might be translated into a truncated protein product (p.(Gln879*)) lacking an important functional domain. The phenotype of our patients included moderate ID, autistic behavior, microcephaly, characteristic facial appearance, EEG abnormalities, hypoplastic corpus callosum, and white matter hypomyelination. Importantly, autistic behavior, facial dysmorphism, and abnormal EEG patterns have been described or investigated only rarely in other reported individuals with biallelic TRAPPC9 changes. Thus, our work highlights the importance of these clinical features in TRAPPC9-related ID. Furthermore, a comprehensive description of clinical features associated with novel TRAPPC9 changes may facilitate genotype-phenotype correlation and offer some clues as to why certain pathogenic variants in theTRAPPC9 gene lead to solely brain-related phenotypes in some patients and syndromic phenotypes in others. Carrier detection molecular testing also was done for nine family members (two unaffected siblings, both parents, three uncles, and both grandmothers).
Strategische Forschungsbereiche und Zentren
- Querschnittsbereich: Medizinische Genetik