Publications by authors named "Anis Khiat"
Article Synopsis
- Integrin alpha V is crucial for cell adhesion and signaling during development, and mutations in its gene (ITGAV) can lead to serious health issues.
- In three families, biallelic variants were found that caused either dysfunctional protein production or the integrin being misplaced, resulting in severe developmental problems like eye and brain abnormalities, inflammatory bowel disease, and immune issues.
- Studies in patient cells and zebrafish models confirmed these mutations resulted in impaired immune signaling and developmental defects, linking the ITGAV variants to a newly identified human disease.
Purpose: Hyper activation of the JAK-STAT signaling underlies the pathophysiology of many human immune-mediated diseases. Herein, the study of 2 adult patients with SOCS1 haploinsufficiency illustrates the severe and pleomorphic consequences of its impaired regulation in the intestinal tract.
Methods: Two unrelated adult patients presented with gastrointestinal manifestations, one with Crohn's disease-like ileo-colic inflammation refractory to anti-TNF and the other with lymphocytic leiomyositis causing severe chronic intestinal pseudo-occlusion.
Mutations in UNC45A, a co-chaperone for myosins, were recently found causative of a syndrome combining cholestasis, diarrhea, loss of hearing and bone fragility. We generated induced pluripotent stem cells (iPSCs) from a patient with a homozygous missense mutation in UNC45A. Cells from this patient, which were reprogrammed using integration-free Sendaï virus, have normal karyotype, express pluripotency markers and are able to differentiate into the three germ cell layers.
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- Scientists discovered that changes in a gene called UNC45A can lead to a health problem that includes diarrhea, deafness, and fragile bones.
- They studied 6 patients and found that their UNC45A gene wasn't working properly, causing issues in their intestines.
- The research showed that UNC45A helps other proteins, like myosin VB, work correctly, and when this gene is missing, it can lead to serious problems in how the intestines are formed and function.
Variants in aminoacyl-tRNA synthetases (ARSs) genes are associated to a broad spectrum of human inherited diseases. Patients with defective PheRS, encoded by FARSA and FARSB, display brain abnormalities, interstitial lung disease and facial dysmorphism. We investigated four children from two unrelated consanguineous families carrying two missense homozygous variants in FARSA with significantly reduced PheRS-mediated aminoacylation activity.
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