title: Compound heterozygous mutations in TTC7A cause familial multiple intestinal atresias and severe combined immunodeficiency.
abstract: Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong.
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong.
authors.forename: P P W
authors.initials: PP
authors.lastname: Lee
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: M-K
authors.initials: MK
authors.lastname: Thong
authors.affiliation: Division of Paediatric Surgery & Paediatric Urology, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: T M
authors.initials: TM
authors.lastname: Ramanujam
authors.affiliation: Division of Paediatric Surgery & Paediatric Urology, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: A
authors.initials: A
authors.lastname: Shanmugam
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: M-T
authors.initials: MT
authors.lastname: Koh
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong.
authors.forename: K-W
authors.initials: KW
authors.lastname: Chan
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong.
authors.forename: D
authors.initials: D
authors.lastname: Ying
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong.
authors.forename: J J
authors.initials: JJ
authors.lastname: Shen
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong.
authors.forename: Y L
authors.initials: YL
authors.lastname: Lau
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007409:Intestinal Atresia / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D016511:Severe Combined Immunodeficiency / Q000235:genetics*
chemical_list: D011506:Proteins; C583818:TTC7A protein, human
keywords: TTC7A; genotype-phenotype correlation; multiple intestinal atresias (MIA); severe combined immunodeficiency (SCID); whole exome sequencing (WES)