Mutations in tetratricopeptide repeat domain 7A (TTC7A) are associated with combined immunodeficiency with dendriform lung ossification but no intestinal atresia
Abstract
Introduction: Genetic aberrations associated with combined immunodeficiency have been increasingly identified in the past two decades. Yet, there are still 30% of these patients with unidentified genetic cause.
Methods: We employed whole genome sequencing to identify the genetic defect leading to combined immunodeficiency. Thymus, gut, and lung tissues were studied using hematoxylin and eosin staining as well as immunohistochemistry.
Results: We identified 2 deleterious mutations in the TTC7A gene. Surprisingly, the patient did not have intestinal atresia but suffered repeated infections as well fatal pneumonitis. Dendriform lung ossification developed, which was unique to this case. The patient had typical presentation of combined immunodeficiency including profound lymphopenia, markedly reduced in-vitro response to mitogens, as well as low TRECS. Serum immunoglobulins were also markedly reduced.
Conclusion: Mutations in the TTC7A gene can cause combined immunodeficiency with no intestinal atresia and predispose to lung ossification.
Statement of novelty: TTC7A mutations can cause profound immunodeficiency without multiple intestinal atresia. We report here for the first time that this defect is associated with dendriform lung ossification.
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Published In
LymphoSign Journal
Volume 01 • Number 01 • September 2014
Pages: 10 - 26
History
Received: 1 May 2014
Accepted: 6 May 2014
Accepted manuscript online: 24 June 2014
Version of record online: 24 June 2014
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NganBo, MericoDaniele, MarcusNufar, KimVy H.D., UptonJulia, BatesAndrea, HerbrickJoanne, NalpathamkalamThomas, ThiruvahindrapuramBhooma, CoxPeter, and RoifmanChaim M.. 2014. Mutations in tetratricopeptide repeat domain 7A (TTC7A) are associated with combined immunodeficiency with dendriform lung ossification but no intestinal atresia. LymphoSign Journal.
01(01): 10-26. https://doi.org/10.14785/lpsn-2014-0002
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