Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ouahed Jodie, Kelsen Judith R, Spessott Waldo A, Kooshesh Kameron, Sanmillan Maria L, Dawany Noor, Sullivan Kathleen E, Hamilton Kathryn E, Slowik Voytek, Nejentsev Sergey, Neves João Farela, Flores Helena, Chung Wendy K, Wilson Ashley, Anyane-Yeboa Kwame, Wou Karen, Jain Preti, Field Michael, Tollefson Sophia, Dent Maiah H, Li Dalin, Naito Takeo, McGovern Dermot P B, Kwong Andrew C, Taliaferro Faith, Ordovas-Montanes Jose, Horwitz Bruce H, Kotlarz Daniel, Klein Christoph, Evans Jonathan, Dorsey Jill, Warner Neil, Elkadri Abdul, Muise Aleixo M, Goldsmith Jeffrey, Thompson Benjamin, Engelhardt Karin R, Cant Andrew J, Hambleton Sophie, Barclay Andrew, Toth-Petroczy Agnes, Vuzman Dana, Carmichael Nikkola, Bodea Corneliu, Cassa Christopher A, Devoto Marcella, Maas Richard L, Behrens Edward M, Giraudo Claudio G, Snapper Scott B
Аннотация
METHODS: Whole exome sequencing was performed on five families with ten patients who presented with a similar constellation of symptoms including medically refractory infantile-onset IBD, bilateral sensorineural hearing loss and, in the majority, recurrent infections. Genetic aetiologies of VEOIBD were assessed and Sanger sequencing was performed to confirm novel genetic findings. Western analysis on peripheral blood mononuclear cells and functional studies with epithelial cell lines were employed.
RESULTS: In each of the ten patients, we identified damaging heterozygous or biallelic variants in the Syntaxin-Binding Protein 3 gene [STXBP3], a protein known to regulate intracellular vesicular trafficking in the syntaxin-binding protein family of molecules, but not associated to date with either VEOIBD or sensorineural hearing loss. These mutations interfere with either intron splicing or protein stability and lead to reduced STXBP3 protein expression. Knock-down of STXBP3 in CaCo2 cells resulted in defects in cell polarity.
CONCLUSION: Overall, we describe a novel genetic syndrome and identify a critical role for STXBP3 in VEOIBD, sensorineural hearing loss and immune dysregulation.