MedElevator
Войти в исследования RNU4ATAC-opathy: Clinical, molecular, and transcriptomic insights from a large cohort.
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.
Matalon Dena R, Duker Angela L, Arriaga Taylor M, Russell Kathryn, Mendez Hector Rodrigo, Bonner Devon E, Harley Margaret E, Singer-Berk Moriel, Wojcik Monica H, Pais Lynn, DiTroia Stephanie, O'Leary Melanie, Cassini Thomas, Ezell Kimberly, Niehaus Anne D, Kaplan Julie, Wargowski David S, Smid Cory J, Longenecker Emily D, Rodriguez Barreto Ana Maria, Miller Danny E, Keefe Alexandra C, Calderwood Laurel, Enns Gregory M, Tekin Mustafa, Bivona Stephanie A, Vora Neeta L, Gilmore Kelly L, Khan Tahir N, Davis Erica E, Wang Amber W, Khan Sameena, Maddirevula Sateesh, Al Abdi Lama, Abuyousef Omar, Shamseldin Hanan E, Alkhalifi Salwa, Abdulwahab Firdous, Alqahtani Mashael, Alhumaidi Zainab A, Nadeef Seba, Al Hashem Amal M, Bakur Khadijah, Faqeih Eissa A, Abdalla Ebtesam, Clarke Angus, Fletcher Elaine, Keng Wee Teik, Ousager Lilian Bomme, de Silva Deepthi C, Haniffa Muzhirah, Mari Francesca, Lam Wayne, Campbell Jennifer, Homfray Tessa, Nampoothiri Sheela, Li Chumei, Chaudhari Bimal P, Truxal Kristen, Genomics Research to Elucidate the Genetics of Rare Diseases consortium, Undiagnosed Diseases Network, Bernstein Jonathan A, Montgomery Stephen B, Wheeler Matthew T, Alkuraya Fowzan S, O'Donnell-Luria Anne, Jackson Andrew P, Campbell Ian M, Ganesh Vijay S, Robertson Nic, Lemire Gabrielle
Аннотация
METHODS: Sixty individuals with molecularly confirmed RNU4ATAC-opathy were recruited from multiple clinical and research centers internationally. RNA-seq was available for 7 affected individuals.
RESULTS: We report the clinical and molecular findings of 60 individuals, including 42 not previously described, and 33 distinct RNU4ATAC variants, 13 of which are novel. Core features in this cohort-present in most individuals assessed and varying in severity-include microcephaly, short stature, skeletal anomalies, developmental delay, cerebral anomalies, skin conditions, and immune deficiency. Additional findings, such as diabetes, holoprosencephaly, and the absence of various core features in some individuals, highlight the broad phenotypic spectrum. All individuals who underwent RNA-seq showed a consistent pattern of minor intron retention. In 6 individuals, RNA-seq enabled the reclassification of variants of uncertain significance as likely pathogenic. Although RNU4ATAC variants are generally covered by clinical exomes, they are often overlooked in analysis because of their noncoding nature.
CONCLUSION: This study highlights the variability of phenotypes and genotypes associated with RNU4ATAC-opathy. Laboratories should ensure RNU4ATAC and other noncoding genes are appropriately assessed by their analysis pipelines.