title: Novel mutations in SKIV2L and TTC37 genes in Malaysian children with trichohepatoenteric syndrome.
abstract: 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.
authors.affiliation: Department of Paediatrics, University Malaya Medical Center, Kuala Lumpur, Malaysia; University Malaya Paediatric and Child Health Research Group, University Malaya Medical Center, Kuala Lumpur, Malaysia.
authors.forename: Way Seah
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Paediatrics, University Malaya Medical Center, Kuala Lumpur, Malaysia.
authors.forename: Kai Ming
authors.initials: KM
authors.lastname: Teo
authors.affiliation: Department of Paediatrics, University Malaya Medical Center, Kuala Lumpur, Malaysia.
authors.forename: Ruey Terng
authors.initials: RT
authors.lastname: Ng
authors.affiliation: Department of Paediatrics, University Malaya Medical Center, Kuala Lumpur, Malaysia.
authors.forename: Sze Yee
authors.initials: SY
authors.lastname: Chong
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Boon Pin
authors.initials: BP
authors.lastname: Kee
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: khchua@um.edu.my.
authors.forename: Kek Heng
authors.initials: KH
authors.lastname: Chua
mesh_terms: D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D018389:Codon, Nonsense; D004265:DNA Helicases / Q000235:genetics*; D003968:Diarrhea, Infantile / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005091:Exons; D019066:Facies; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D016368:Frameshift Mutation; D006201:Hair Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; C550452:TTC37 protein, human; D004265:DNA Helicases; C114718:SKIV2L protein, human
keywords: Diarrhea; SKIV2L; TTC37; Trichohepatoenteric syndrome