Targeted gene panel sequencing in children with very early onset inflammatory bowel disease—evaluation and prospective analysis

Kammermeier, Jochen; Drury, Suzanne; James, Chela; Dziubak, Robert; Ocaka, Louise; Elawad, Mamoun; Beales, Philip L.; Lench, Nicholas; Uhlig, Holm H.; Bacchelli, Chiara; Shah, Neil

doi:10.1136/jmedgenet-2014-102624

Cited by 87 publications

(90 citation statements)

References 30 publications

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“…In one patient (33) there were no details and it was before HSCT. It should be noted that the patients with partial effect presented with some aspect of IBD-like SD/THE (17,26,27,32). In some cases steroids were given in combination with immunosuppressant drugs.…”

Section: Steroidsmentioning

confidence: 99%

“…Thus, some patients were given multiple drugs, either sequentially or at the same time. Summing up: 5 ASA was used four times with no effect in three patients (17,27) and one case of partial amelioration in combination with steroids (27). Azathioprine was used 5 times, with no effect in 4 patients (4,17,26) and possibly a partial amelioration in one (26).…”

Section: Immunosuppressant Drugsmentioning

confidence: 99%

“…Seven drugs were used for a combined total of 24 times in 13 patients (4,17,26,27,30,32,33). Thus, some patients were given multiple drugs, either sequentially or at the same time.…”

Section: Immunosuppressant Drugsmentioning

confidence: 99%

“…Methotrexate was used in one patient (17) with no effect. Sirolimus was used in 2 patients without effect, Tacrolimus was used twice in 3 patients without any effect (17,26) and one before HSCT (33). Anti-TNF antibody was used in 7 patients; for one there was no description of outcome (33), for 2 (17) there was no improvement, for 3 there was a partial and inconsistant improvement (26,27,32).…”

Section: Immunosuppressant Drugsmentioning

confidence: 99%

“…Steroids were administered to 17 patients (4,17,23,26,27,30,(32)(33)(34). No effect was reported in 11 patients and in 5 patients only a partial amelioration was noted.…”

Section: Steroidsmentioning

confidence: 99%

See 4 more Smart Citations

Management of syndromic diarrhea/tricho-hepato-enteric syndrome: A review of the literature

Fabre

Bourgeois

Coste

et al. 2017

IRDR

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Section: Steroidsmentioning

confidence: 99%

Section: Immunosuppressant Drugsmentioning

confidence: 99%

“…Seven drugs were used for a combined total of 24 times in 13 patients (4,17,26,27,30,32,33). Thus, some patients were given multiple drugs, either sequentially or at the same time.…”

Section: Immunosuppressant Drugsmentioning

confidence: 99%

Section: Immunosuppressant Drugsmentioning

confidence: 99%

“…Steroids were administered to 17 patients (4,17,23,26,27,30,(32)(33)(34). No effect was reported in 11 patients and in 5 patients only a partial amelioration was noted.…”

Section: Steroidsmentioning

confidence: 99%

See 3 more Smart Citations

Management of syndromic diarrhea/tricho-hepato-enteric syndrome: A review of the literature

Fabre

Bourgeois

Coste

et al. 2017

IRDR

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Physiology of Electrolyte Transport in the Gut: Implications for Disease

Rao

2019

Comprehensive Physiology

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We now have an increased understanding of the genetics, cell biology, and physiology of electrolyte transport processes in the mammalian intestine, due to the availability of sophisticated methodologies ranging from genome wide association studies to CRISPR‐CAS technology, stem cell‐derived organoids, 3D microscopy, electron cryomicroscopy, single cell RNA sequencing, transgenic methodologies, and tools to manipulate cellular processes at a molecular level. This knowledge has simultaneously underscored the complexity of biological systems and the interdependence of multiple regulatory systems. In addition to the plethora of mammalian neurohumoral factors and their cross talk, advances in pyrosequencing and metagenomic analyses have highlighted the relevance of the microbiome to intestinal regulation. This article provides an overview of our current understanding of electrolyte transport processes in the small and large intestine, their regulation in health and how dysregulation at multiple levels can result in disease. Intestinal electrolyte transport is a balance of ion secretory and ion absorptive processes, all exquisitely dependent on the basolateral Na + /K + ATPase; when this balance goes awry, it can result in diarrhea or in constipation. The key transporters involved in secretion are the apical membrane Cl − channels and the basolateral Na + ‐K + ‐2Cl − cotransporter, NKCC1 and K + channels. Absorption chiefly involves apical membrane Na + /H + exchangers and Cl − /HCO 3 − exchangers in the small intestine and proximal colon and Na + channels in the distal colon. Key examples of our current understanding of infectious, inflammatory, and genetic diarrheal diseases and of constipation are provided. © 2019 American Physiological Society. Compr Physiol 9:947‐1023, 2019.

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Determination of disease phenotypes and pathogenic variants from exome sequence data in the CAGI 4 gene panel challenge

et al. 2017

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The use of gene panel sequence for diagnostic and prognostic testing is now widespread, but there are so far few objective tests of methods to interpret these data. We describe the design and implementation of a gene panel sequencing data analysis pipeline (VarP) and its assessment in a CAGI4 community experiment. The method was applied to clinical gene panel sequencing data of 106 patients, with the goal of determining which of 14 disease classes each patient has and the corresponding causative variant(s). The disease class was correctly identified for 36 cases, including 10 where the original clinical pipeline did not find causative variants. For a further seven cases, we found strong evidence of an alternative disease to that tested. Many of the potentially causative variants are missense, with no previous association with disease, and these proved the hardest to correctly assign pathogenicity or otherwise. Post analysis showed that three-dimensional structure data could have helped for up to half of these cases. Over-reliance on HGMD annotation led to a number of incorrect disease assignments. We used a largely ad hoc method to assign probabilities of pathogenicity for each variant, and there is much work still to be done in this area.

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Targeted gene panel sequencing in children with very early onset inflammatory bowel disease—evaluation and prospective analysis

Cited by 87 publications

References 30 publications

Management of syndromic diarrhea/tricho-hepato-enteric syndrome: A review of the literature

Management of syndromic diarrhea/tricho-hepato-enteric syndrome: A review of the literature

Physiology of Electrolyte Transport in the Gut: Implications for Disease

Determination of disease phenotypes and pathogenic variants from exome sequence data in the CAGI 4 gene panel challenge

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