MedElevator Войти в исследования
← Поиск публикаций

DOI 10.1016/j.gim.2021.09.001

Медицинская библиотека · Genetics in medicine : official journal of the American College of Medical Genetics · 2021

Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants.

Bournazos Adam M, Riley Lisa G, Bommireddipalli Shobhana, Ades Lesley, Akesson Lauren S, Al-Shinnag Mohammad, Alexander Stephen I, Archibald Alison D, Balasubramaniam Shanti, Berman Yemima, Beshay Victoria, Boggs Kirsten, Bojadzieva Jasmina, Brown Natasha J, Bryen Samantha J, Buckley Michael F, Chong Belinda, Davis Mark R, Dawes Ruebena, Delatycki Martin, Donaldson Liz, Downie Lilian, Edwards Caitlin, Edwards Matthew, Engel Amanda, Ewans Lisa J, Faiz Fathimath, Fennell Andrew, Field Michael, Freckmann Mary-Louise, Gallacher Lyndon, Gear Russell, Goel Himanshu, Goh Shuxiang, Goodwin Linda, Hanna Bernadette, Harraway James, Higgins Megan, Ho Gladys, Hopper Bruce K, Horton Ari E, Hunter Matthew F, Huq Aamira J, Josephi-Taylor Sarah, Joshi Himanshu, Kirk Edwin, Krzesinski Emma, Kumar Kishore R, Lemckert Frances, Leventer Richard J, Lindsey-Temple Suzanna E, Lunke Sebastian, Ma Alan, Macaskill Steven, Mallawaarachchi Amali, Marty Melanie, Marum Justine E, McCarthy Hugh J, Menezes Manoj P, McLean Alison, Milnes Di, Mohammad Shekeeb, Mowat David, Niaz Aram, Palmer Elizabeth E, Patel Chirag, Patel Shilpan G, Phelan Dean, Pinner Jason R, Rajagopalan Sulekha, Regan Matthew, Rodgers Jonathan, Rodrigues Miriam, Roxburgh Richard H, Sachdev Rani, Roscioli Tony, Samarasekera Ruvishani, Sandaradura Sarah A, Savva Elena, Schindler Tim, Shah Margit, Sinnerbrink Ingrid B, Smith Janine M, Smith Richard J, Springer Amanda, Stark Zornitza, Strom Samuel P, Sue Carolyn M, Tan Kenneth, Tan Tiong Y, Tantsis Esther, Tchan Michel C, Thompson Bryony A, Trainer Alison H, van Spaendonck-Zwarts Karin, Walsh Rebecca, Warwick Linda, White Stephanie, White Susan M, Williams Mark G, Wilson Meredith J, Wong Wui Kwan, Wright Dale C, Yap Patrick, Yeung Alison, Young Helen, Jones Kristi J, Bennetts Bruce, Cooper Sandra T, Australasian Consortium for RNA Diagnostics

СтатьяПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

PURPOSE: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy).

METHODS

A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases.

RESULTS

Informative RNA assay data were obtained for 96% of cases, enabling variant reclassification for 75% variants that can be used for genetic counseling (71%), to inform clinical care (32%) and prenatal counseling (41%). Variant-associated mis-splicing was highly reproducible for 28 cases with samples from ≥2 affected individuals or heterozygotes and 10 cases with ≥2 biospecimens. PCR amplicons encompassing another segregated heterozygous variant was vital for clinical interpretation of 22 of 79 variants to phase RNA splicing events and discern complete from partial mis-splicing.

CONCLUSION

RNA diagnostics enabled provision of a genetic diagnosis for 64% of recruited cases. PCR-based RNA diagnostics has capacity to analyze 81.3% of clinically significant genes, with long amplicons providing an advantage over RNA sequencing to phase RNA splicing events. The Australasian Consortium for RNA Diagnostics (SpliceACORD) provide clinically-endorsed, standardized protocols and recommendations for interpreting RNA assay data.

Для цитирования: Bournazos Adam M, Riley Lisa G, Bommireddipalli Shobhana, Ades Lesley, Akesson Lauren S, Al-Shinnag Mohammad, Alexander Stephen I, Archibald Alison D, Balasubramaniam Shanti, Berman Yemima, Beshay Victoria, Boggs Kirsten, Bojadzieva Jasmina, Brown Natasha J, Bryen Samantha J, Buckley Michael F, Chong Belinda, Davis Mark R, Dawes Ruebena, Delatycki Martin, Donaldson Liz, Downie Lilian, Edwards Caitlin, Edwards Matthew, Engel Amanda, Ewans Lisa J, Faiz Fathimath, Fennell Andrew, Field Michael, Freckmann Mary-Louise, Gallacher Lyndon, Gear Russell, Goel Himanshu, Goh Shuxiang, Goodwin Linda, Hanna Bernadette, Harraway James, Higgins Megan, Ho Gladys, Hopper Bruce K, Horton Ari E, Hunter Matthew F, Huq Aamira J, Josephi-Taylor Sarah, Joshi Himanshu, Kirk Edwin, Krzesinski Emma, Kumar Kishore R, Lemckert Frances, Leventer Richard J, Lindsey-Temple Suzanna E, Lunke Sebastian, Ma Alan, Macaskill Steven, Mallawaarachchi Amali, Marty Melanie, Marum Justine E, McCarthy Hugh J, Menezes Manoj P, McLean Alison, Milnes Di, Mohammad Shekeeb, Mowat David, Niaz Aram, Palmer Elizabeth E, Patel Chirag, Patel Shilpan G, Phelan Dean, Pinner Jason R, Rajagopalan Sulekha, Regan Matthew, Rodgers Jonathan, Rodrigues Miriam, Roxburgh Richard H, Sachdev Rani, Roscioli Tony, Samarasekera Ruvishani, Sandaradura Sarah A, Savva Elena, Schindler Tim, Shah Margit, Sinnerbrink Ingrid B, Smith Janine M, Smith Richard J, Springer Amanda, Stark Zornitza, Strom Samuel P, Sue Carolyn M, Tan Kenneth, Tan Tiong Y, Tantsis Esther, Tchan Michel C, Thompson Bryony A, Trainer Alison H, van Spaendonck-Zwarts Karin, Walsh Rebecca, Warwick Linda, White Stephanie, White Susan M, Williams Mark G, Wilson Meredith J, Wong Wui Kwan, Wright Dale C, Yap Patrick, Yeung Alison, Young Helen, Jones Kristi J, Bennetts Bruce, Cooper Sandra T, Australasian Consortium for RNA Diagnostics. Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants.. Genetics in medicine : official journal of the American College of Medical Genetics. 2021. DOI: 10.1016/j.gim.2021.09.001.

Предметные рубрики MeSH

AdolescentAdultChild, PreschoolHumansMutationRNARNA SplicingSequence Analysis, RNAExome Sequencing
Подготовка и перевод публикации
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…

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.

Тип публикации указан по данным источника. Уровень доказательности автоматически не присваивается.