Novel mutations in SKIV2L and TTC37 genes in Malaysian children with trichohepatoenteric syndrome

• We reported novel mutations in SKIV2L and TTC37 genes in Malaysian THES patients.
• Three point mutations were observed, i.e., one nonsense, one frameshift, and one missense.
• All point mutations, i.e., c.1891G > A, c.3187C > T, and c.3426dupA, were predicted to be pathogenic to the protein structure.

Trichohepatoenteric syndrome (THES) is a rare autosomal recessive disorder that is classically associated with intractable diarrhea with an onset within the first few months of life. Herein, we investigated and reported novel mutations in two causal genes in 3 Malaysian cases. Genomic DNA was extracted from peripheral blood obtained from patients in two Malaysian Chinese families. The exons of SKIV2L and TTC37 genes were amplified and sequenced by bi-directional sequencing to identify the point mutations within the coding sequence. Three Chinese boys from two families with characteristic features and clinical course were diagnosed with THES. In family-1, two point mutations were identified in the SKIV2L gene (c.1891G > A and c.3187C > T). In family-2, a single-nucleotide duplication (c.3426dupA) was found in the TTC37 gene. These mutations cause the production of abnormal non-functional gene product leading to the clinical manifestations in the patients. We reported three point mutations, which have not been previously described in other patients with THES in SKIV2L and TTC37 genes, including one nonsense, one frameshift, and one missense mutations.