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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Whole-exome sequencing identifies tetratricopeptide repeat domain 7A (TTC7A) mutations for combined immunodeficiency with intestinal atresias
Journal of Allergy and Clinical Immunology, Volume 132, No. 3, Year 2013
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Description
Background Combined immunodeficiency with multiple intestinal atresias (CID-MIA) is a rare hereditary disease characterized by intestinal obstructions and profound immune defects. Objective We sought to determine the underlying genetic causes of CID-MIA by analyzing the exomic sequences of 5 patients and their healthy direct relatives from 5 unrelated families. Methods We performed whole-exome sequencing on 5 patients with CID-MIA and 10 healthy direct family members belonging to 5 unrelated families with CID-MIA. We also performed targeted Sanger sequencing for the candidate gene tetratricopeptide repeat domain 7A (TTC7A) on 3 additional patients with CID-MIA. Results Through analysis and comparison of the exomic sequence of the subjects from these 5 families, we identified biallelic damaging mutations in the TTC7A gene, for a total of 7 distinct mutations. Targeted TTC7A gene sequencing in 3 additional unrelated patients with CID-MIA revealed biallelic deleterious mutations in 2 of them, as well as an aberrant splice product in the third patient. Staining of normal thymus showed that the TTC7A protein is expressed in thymic epithelial cells, as well as in thymocytes. Moreover, severe lymphoid depletion was observed in the thymus and peripheral lymphoid tissues from 2 patients with CID-MIA. Conclusions We identified deleterious mutations of the TTC7A gene in 8 unrelated patients with CID-MIA and demonstrated that the TTC7A protein is expressed in the thymus. Our results strongly suggest that TTC7A gene defects cause CID-MIA. © 2013 American Academy of Allergy, Asthma & Immunology.
Authors & Co-Authors
Chen, Rui
United States, Stanford
Stanford University School of Medicine
Giliani, S.
United States, Stanford
Stanford University School of Medicine
Lanzi, Gaetana
United States, Stanford
Stanford University School of Medicine
Mias, George I.
United States, Stanford
Stanford University School of Medicine
Lonardi, Silvia
Italy, Brescia
Università Degli Studi Di Brescia
Dobbs, Kerry
Italy, Brescia
Università Degli Studi Di Brescia
Manis, John P.
United States, Boston
Boston Children's Hospital
Im, Hogune
United States, Stanford
Stanford University School of Medicine
Gallagher, Jennifer E.G.
United States, Stanford
Stanford University School of Medicine
Phanstiel, Douglas H.
United States, Stanford
Stanford University School of Medicine
Euskirchen, Ghia M.
United States, Stanford
Stanford University School of Medicine
Lacroute, Phil G.
United States, Stanford
Stanford University School of Medicine
Bettinger, Keith E.
United States, Stanford
Stanford University School of Medicine
Moratto, Daniele
United States, Stanford
Stanford University School of Medicine
Weinacht, Katja Gabriele
United States, Boston
Boston Children's Hospital
Montin, Davide
United States, Boston
Boston Children's Hospital
Gallo, Eleonora
United States, Boston
Boston Children's Hospital
Mangili, Giovanna
United States, Boston
Boston Children's Hospital
Porta, Fulvio A.
Italy, Turin
Università Degli Studi Di Torino
Notarangelo, Lucia Dora
Italy, Turin
Università Degli Studi Di Torino
Pedretti, Stefania
Italy, Bergamo
Ospedali Riuniti Di Bergamo
Al-Herz, Waleed
Italy, Brescia
Spedali Civili Di Brescia
Alfahdli, Wasmi
Italy, Brescia
Spedali Civili Di Brescia
Comeau, Anne Marie
Kuwait
Al-sabah Hospital
Traister, Russell S.
Kuwait, Safat
Ibn Sina Hospital Safat
Pai, Sung-yun
United States, Worcester
University of Massachusetts Chan Medical School
Carella, Graziella
United States, Pittsburgh
Upmc Children’s Hospital of Pittsburgh
Facchetti, Fabio
Italy, Brescia
Università Degli Studi Di Brescia
Nadeau, Kari Christine
United States, Cambridge
Harvard Stem Cell Institute
Snyder, Michael Paul
United States, Stanford
Stanford University School of Medicine
Notarangelo, Luigi Daniele
Italy, Brescia
Università Degli Studi Di Brescia
United States, Cambridge
Harvard Stem Cell Institute
Statistics
Citations: 144
Authors: 31
Affiliations: 11
Identifiers
Doi:
10.1016/j.jaci.2013.06.013
ISSN:
00916749
e-ISSN:
10976825
Research Areas
Genetics And Genomics
Health System And Policy