TTC7A: Steward of Intestinal Health

Jardine, Sasha; Dhingani, Neel; Muise, Aleixo M.

doi:10.1016/j.jcmgh.2018.12.001

Cited by 57 publications

(79 citation statements)

References 71 publications

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“…Less than 10% patients of TTC7A mutation manifest as VEOIBD with secretory diarrhea, chronic intestinal inflammation, lymphocytopenia, and/or hypoglobulinemia, etc [15,20]. VEOIBD is more likely to presents with isolated colonic involvement and paucity of ileal involvement.…”

Section: Discussionmentioning

confidence: 99%

“…VEOIBD is poor response to steroids, immunosuppressives, and biologics [15]. Hematopoietic stem cell transplantation was reported in monogenic IBD, which may restore immunity and increase survival in immunodeficiency patients, but it does not seem to improve phenotypes associated with intestinal epithelial defects [15]. The survival rate of TTC7A deficiency treated with hematopoietic stem cell transplantation was not improved [32,34].…”

Section: Discussionmentioning

confidence: 99%

“…But to date, it remains difficult to form a significant genotype/phenotype correlation. Jardine S found most cases were diagnosed within one year after birth, only 2 cases were diagnosed in neonatal period [15]. Neonatal onset IBD often has poor response to conventional treatments in contrast to adult onset IBD [16].…”

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confidence: 99%

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Phenotype and genotype characteristics of neonatal onset inflammatory bowel disease with combined immunodeficiency of TTC7A deficiency in mainland China

Chen¹,

Chen²,

Guo³

et al. 2021

Preprint

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Objective: To explore the characteristics of genotype and phenotype of neonatal onset inflammatory bowel disease with combined immunodeficiency caused by a novel TTC7A mutant. Methods: We summarized the clinical manifestations, imagings, endoscopic and histological findings, biochemical analyses,whole exon sequencing(WES), in silico and intervention of the patient. Results: The boy showed severe diarrhea, malnutrition, electrolyte disturbance, dehydration and recurrent infections after birth. X-ray and ultrasonic images displayed no specific changes. Endoscopic and histological findings showed chronic inflammation. Immune functions indicated combined immunodeficiency. WES identified compound heterozygote TTC7A mutations c.2355+4A>G/c.643G>T in the infant. No abnormal splicing sequence by c.2355+4A>G mutation was found in TTC7A expression analysis, but the mRNA expression decreased. There was no improvement after treatment with methylprednisolone and leflunomide. The infant died when he was given up at 5 months 19 days old. Conclusion: The compound heterozygote mutations (c.2355+4A>G, c.643G>T) in TTC7A gene were firstly described and confirmed. Our report expands the phenotypic spectrum of TTC7A mutaions and genotypic spectrum of very early onset inflammatory bowel disease with combined immunodeficiency.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Phenotype and genotype characteristics of neonatal onset inflammatory bowel disease with combined immunodeficiency of TTC7A deficiency in mainland China

Chen¹,

Chen²,

Guo³

et al. 2021

Preprint

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“…HSCT cures interleukin-10 (IL10) signalling defects causing IBD. 4 In contrast, it does not improve intestinal inflammation in TTC7A deficiency, 16 a disease manifesting with IBD, intestinal atresia and immunodeficiency. Similarly, in NEMO-deficient patients caused by defects in IKBKG , HSCT resolves the immunodeficiency but does not cure intestinal inflammation.…”

Section: Introductionmentioning

confidence: 99%

Remission of Inflammatory Bowel Disease in Glucose-6-Phosphatase 3 Deficiency by Allogeneic Haematopoietic Stem Cell Transplantation

Bolton

Burch

Morgan

et al. 2019

Journal of Crohn's and Colitis

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Mendelian disorders in glucose-6-phosphate metabolism can present with inflammatory bowel disease [IBD]. Using whole genome sequencing we identified a homozygous variant in the glucose-6-phosphatase G6PC3 gene [c.911dupC; p.Q305fs*82] in an adult patient with congenital neutropenia, lymphopenia and childhood-onset, therapy-refractory Crohn’s disease. Because G6PC3 is expressed in several haematopoietic and non-haematopoietic cells it was unclear whether allogeneic stem cell transplantation [HSCT] would benefit this patient with intestinal inflammation. We show that HSCT resolves G6PC3-associated immunodeficiency and the Crohn’s disease phenotype. It illustrates how even in adulthood, next-generation sequencing can have a significant impact on clinical practice and healthcare utilization in patients with immunodeficiency and monogenic IBD.

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“…Previously, we and others identified TTC7A deficiency as a cause of severe intestinal disease 1 , 13 – 18 . Over 50 patients have been identified with pathogenic variants in TTC7A associated with a heterogeneous array of phenotypes involving the intestine and immune system 1 , 13 – 25 . VEOIBD patients with TTC7A variants have apoptotic enterocolitis and functional studies show loss of interaction with Phosphatidylinositol 4-kinase Type III Alpha (PI4KIIIα) to be the causative factor 1 .…”

Section: Introductionmentioning

confidence: 99%

The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease

Dhingani

Guo

Pan

et al. 2020

Sci Rep

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Very early onset inflammatory bowel disease (VEOIBD) denotes children with onset of IBD before six years of age. A number of monogenic disorders are associated with VEOIBD including tetratricopeptide repeat domain 7A (TTC7A) deficiency. TTC7A-deficiency is characterized by apoptotic colitis in milder cases with severe intestinal atresia and immunodeficiency in cases with complete loss of protein. We used whole exome sequencing in a VEOIBD patient presenting with colitis characterized by colonic apoptosis and no identified known VEOIBD variants, to identify compound heterozygous deleterious variants in the Ubiquitin protein ligase E3 component N-recognin 5 (UBR5) gene. Functional studies demonstrated that UBR5 co-immunoprecipitates with the TTC7A and the UBR5 variants had reduced interaction between UBR5 and TTC7A. Together this implicates UBR5 in regulating TTC7A signaling in VEOIBD patients with apoptotic colitis.

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TTC7A: Steward of Intestinal Health

Cited by 57 publications

References 71 publications

Phenotype and genotype characteristics of neonatal onset inflammatory bowel disease with combined immunodeficiency of TTC7A deficiency in mainland China

Phenotype and genotype characteristics of neonatal onset inflammatory bowel disease with combined immunodeficiency of TTC7A deficiency in mainland China

Remission of Inflammatory Bowel Disease in Glucose-6-Phosphatase 3 Deficiency by Allogeneic Haematopoietic Stem Cell Transplantation

The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease

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