Bialellic Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) Cause Common Variable Immunodeficiency-Like Phenotype with Enteropathy

Lawless, Dylan; Mistry, Anoop; Wood, Philip; Stahlschmidt, Jens; Arumugakani, Gururaj; Anwar, Rashida; Carter, Clive; Savic, Sinisa

doi:10.1007/s10875-017-0427-1

Cited by 18 publications

(13 citation statements)

References 15 publications

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“…Samuels et al 1 based DNA annotations on NC_000002.11 because one of the mutations affected an intronic region, however, the protein annotation was based on NP_065191.2. To our knowledge, the remaining 62, 4, 7, 10, 12, 14 publications did not report the National Center for Biotechnology Information coding sequence and protein reference codes.bSurviving patient age is as reported in the original publication.cMaternal.…”

Section: Underlying Genetics Of Ttc7a Deficiencymentioning

confidence: 99%

“…To understand the effects of specific TTC7A mutations that contribute to complete loss of protein function, more protein analysis via immunostaining or immunoblotting is required. For example, protein analysis was limited among the 15 publications discussed here: 3 provided TTC7A immunohistochemical staining of the thymus, 2 small bowel, 12 and cecum, 3 and 2 provided immunoblot protein analysis from TTC7A mutant overexpression cell lines 3, 8. To fully appreciate the pathogenicity of specific TTC7A mutations, site-specific and knock-in mutagenesis studies in disease models will aid in understanding the relationship between genetics and disease phenotypes.…”

Section: Underlying Genetics Of Ttc7a Deficiencymentioning

confidence: 99%

“…Rare autosomal-recessive variants in tetratricopeptide repeat domain 7A ( TTC7A ) have been discovered in patients presenting with severe intestinal and immune diseases 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. Mounting evidence has indicated that TTC7A mutations can result in various phenotypes that may or may not be associated with combined immunodeficiency (CID), including multiple intestinal atresias (MIA) and very early onset inflammatory bowel disease (VEOIBD), a form of IBD in children younger than 6 years of age 3, 5, 13.…”

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confidence: 99%

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TTC7A: Steward of Intestinal Health

Jardine

Dhingani

Muise

2019

Cellular and Molecular Gastroenterology and Hepatology

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Section: Underlying Genetics Of Ttc7a Deficiencymentioning

confidence: 99%

Section: Underlying Genetics Of Ttc7a Deficiencymentioning

confidence: 99%

mentioning

confidence: 99%

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TTC7A: Steward of Intestinal Health

Jardine

Dhingani

Muise

2019

Cellular and Molecular Gastroenterology and Hepatology

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“…48 There have been cases of severe intestinal disease in older patients with compound heterozygous mutations in TTC7A . 49 Although the mechanism of disease seen in TTC7A defects has not been fully elucidated, the protein appears to repress RhoA signaling. Therefore, mutations lead to increased rho kinase activity, disrupting epithelial intestinal cell polarity and growth with subsequent multiple intestinal atresia and impairment of immune cell homeostasis resulting in combined immunodeficiency.…”

Section: Unique Genomics Of Veo-ibdmentioning

confidence: 99%

Genomic and Immunologic Drivers of Very Early-Onset Inflammatory Bowel Disease

Conrad

Kelsen

2019

Pediatr Dev Pathol

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Purpose of Review: Inflammatory bowel disease (IBD) is a multifactorial disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. However, a subset of patients with IBD diagnosed <6 years of age, known as very early-onset (VEO)-IBD, can be phenotypically and genetically distinct from older onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to the underlying genomic and immunologic drivers of disease, and the significant impact on our therapeutic decisions. Recent Findings: VEO-IBD is increasing in incidence and is associated with more severe disease, aggressive progression, and poor response to most conventional therapies. This article will review some of the genetic findings in this population and the subsequent impact on therapy, with targeted approaches. Summary: Children with VEO-IBD may present with a different phenotype and more severe disease than older children and adults. An integrated approach combining genetics, immunology, and traditional IBD evaluations can lead to the identification of causal defects that directly impact management. These strategies can also be employed in older onset refractory IBD.

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“…The prognosis is poor and most patients die at a young age. More recently, a milder phenotype of enteropathy and predominantly humoral immunodeficiency has been reported ( 315 ).…”

Section: Ttc7a Deficiencymentioning

confidence: 99%

Bacille Calmette–Guerin Complications in Newly Described Primary Immunodeficiency Diseases: 2010–2017

Nunes-Santos

Rosenzweig

2018

Front. Immunol.

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Bacille Calmette–Guerin (BCG) vaccine is widely used as a prevention strategy against tuberculosis. BCG is a live vaccine, usually given early in life in most countries. While safe to most recipients, it poses a risk to immunocompromised patients. Several primary immunodeficiency diseases (PIDD) have been classically associated with complications related to BCG vaccine. However, a number of new inborn errors of immunity have been described lately in which little is known about adverse reactions following BCG vaccination. The aim of this review is to summarize the existing data on BCG-related complications in patients diagnosed with PIDD described since 2010. When BCG vaccination status or complications were not specifically addressed in those manuscripts, we directly contacted the corresponding authors for further clarification. We also analyzed data on other mycobacterial infections in these patients. Based on our analysis, around 8% of patients with gain-of-function mutations in STAT1 had mycobacterial infections, including localized complications in 3 and disseminated disease in 4 out of 19 BCG-vaccinated patients. Localized BCG reactions were also frequent in activated PI3Kδ syndrome type 1 (3/10) and type 2 (2/18) vaccinated children. Also, of note, no BCG-related complications have been described in either CTLA4 or LRBA protein-deficient patients; and not enough information on BCG-vaccinated NFKB1 or NFKB2-deficient patients was available to drive any conclusions about these diseases. Despite the high prevalence of environmental mycobacterial infections in GATA2-deficient patients, only one case of BCG reaction has been reported in a patient who developed disseminated disease. In conclusion, BCG complications could be expected in some particular, recently described PIDD and it remains a preventable risk factor for pediatric PIDD patients.

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Bialellic Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) Cause Common Variable Immunodeficiency-Like Phenotype with Enteropathy

Cited by 18 publications

References 15 publications

TTC7A: Steward of Intestinal Health

TTC7A: Steward of Intestinal Health

Genomic and Immunologic Drivers of Very Early-Onset Inflammatory Bowel Disease

Bacille Calmette–Guerin Complications in Newly Described Primary Immunodeficiency Diseases: 2010–2017

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