Kerith-Rae Dias, Rupendra Shrestha, Deborah Schofield, Carey-Anne Evans, Emily O'Heir, Ying Zhu, Futao Zhang, Krystle Standen, Ben Weisburd, Sarah L Stenton, Alba Sanchis-Juan, Harrison Brand, Michael E Talkowski, Alan Ma, Sondy Ghedia, Meredith Wilson, Sarah A Sandaradura, Janine Smith, Benjamin Kamien, Anne Turner, Madhura Bakshi, Lesley C Adès, David Mowat, Matthew Regan, George McGillivray, Ravi Savarirayan, Susan M White, Tiong Yang Tan, Zornitza Stark, Natasha J Brown, Luis A Pérez-Jurado, Emma Krzesinski, Matthew F Hunter, Lauren Akesson, Andrew Paul Fennell, Alison Yeung, Tiffany Boughtwood, Lisa Ewans, Jennifer Kerkhof, Christopher Lucas, Louise Carey, Hugh French, Melissa Rapadas, Igor Stevanovski, Ira W Deveson, Corrina Cliffe, George Elakis, Edwin P Kirk, Tracy Dudding-Byth, Janice Fletcher, Rebecca Walsh, Mark A Corbett, Thessa Kroes, Jozef Gecz, Cliff Meldrum, Simon Cliffe, Meg Wall, Sebastian Lunke, Kathryn North, David J Amor, Michael Field, Bekim Sadikovic, Michael F Buckley, Anne O'Donnell-Luria, Tony Roscioli
PURPOSE: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively. METHODS: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID. RESULTS: The ES diagnostic yield was 42/74 (57%). GS diagnoses were made in 9/32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8/9 SNVs/CNVs undetected in older ES, confirming a GS-unique diagnostic rate of 1/32 (3%)...
January 19, 2024: Genetics in Medicine: Official Journal of the American College of Medical Genetics