TARGETED NEXT-GENERATION SEQUENCING ANALYSIS OF 1,000 INDIVIDUALS WITH INTELLECTUAL DISABILITY
- Grozeva D, Carss K, Spasic-Boskovic O, Tejada MI, Gecz J, Shaw M, Corbett M, Haan E, Thompson E, Friend K, Hussain Z, Hackett A, Field M, Renieri A, Stevenson R, Schwartz C, Floyd JA, Bentham J, Cosgrove C, Keavney B, Bhattacharya S
- Italian X-linked Mental Retardation Project
- UK10K Consortium
- GOLD Consortium, Hurles M, Raymond FL. Strangoni G, D' Avanzo G, Carnevale F, Resta N, Scarano G, Mazzanti L, Borgatti R, Parini B, Marchina E, Strisciuglio P, Cavalli P, Bigoni S, Zammarchi E, Faravelli F, Di Rocco M, Lerone M, Gaslini G, D'Alessandro E, Selicorni A, Pantaleoni C, Bedeschi F, Rinaldi MM, Tenconi R, Verri A, Battaglia A, Guerrini R, Priolo M, Garavelli L, Neri G, Pergola M, Galasso C, Zelante L, Renieri A, Ferrero G, Memo L, Turolla L, Hladnik U, Romano C, Durbin R, Barrett J, Barroso I, Davey-Smith G, Farooqi IS, Hurles M, O' Rahilly S, Palotie A, Soranzo N, Spector T, Zeggini E, Beales P, Bentham J, Bhattacharya S, Blackwood D, Bolton P, Breen G, Chatterjee K, Collier D, Fitzpatrick D, Gallagher L, Geschwind D, Gurling H, Humphries S, McGuffin P, Monaco A, Muntoni F, Owen M, Raymond L, Savage D, Scambler P, Semple R, Skuse D, St Clair D, Timpson N, Van der Aa N, Ahmed A, Ajith VK, Archer H, Armstrong R, Balasubramanian M, Baralle D, Barnicoat A, Beales P, Bennett C, Bernhard B, Bianciardi L, Bitner-Glindzicz M, Blair E, van Bokhoven H, van Bon B, Bradley L, Brady A, Brewer C, Brunner H, Burke M, Caliebe A, Canham N, Castle B, Chandler K, Clarke A, Clayton-Smith J, Clowes V, Cole T, Collins A, Cook J, Coughlin C, Cowe A, Cox H, Crow Y, Dabir T, Davies S, Deshpande D, Diderich KE, Dolling C, Donnai D, Donnelly D, Dooijes D, Dupont J, Ellis I, Van Esch H, Field M, De Filippis R, Firth H, Fisher R, Fitzpatrick D, Foulds N, Franco B, Fry A, Fryer A, Fuchs G, Garcia S, Gardiner C, Gecz J, Gibbons R, Goodship J, Green A, Greenhalgh L, Guanti G, Guilbert P, Hackett A, Halest MV, Haroon M, Harvey J, Henderson A, Hennekam R, Holden S, Holder S, Homfray T, Hurst J, Ionnides A, Jarvis J, Johnson DS, Jones E, Jones L, Jones L, Jongmans M, Josifova D, Joss S, Kenny J, Kerr B, Kingston H, Kini U, Kivuva E, Kooy F, Kraus A, Kurian M, Lachlan K, Lam W, Lees M, Lindsay S, Longman C, Lynch S, Magee A, Van Maldergem L, Male A, Mari F, McConnell V, McGeb A, McKee S, McKeown C, McWilliam C, Medeira A, Mehta S, Metcalfe K, Mohammed S, Morton J, Murday V, Newbury-Ecob R, Nik-Zainal' S, Norman A, Park SM, Parker MJ, Prescott K, Price S, Procter A, Quarrell O, Rankin J, Raymond L, Rea G, Reardon W, Renieri A, Robert L, Rosser E, Sandford R, Schwartz C, Scott R, Scurr I, Senger G, Sharif S, Shaw A, Shaw C, Shears D, Smithson S, Splitt M, Stevenson R, Stewart A, Stewart F, Stewart H, Suri M, Sweeney E, Taffinder S, Tanteles G, Tejada MI, Temple K, Thompson J, Tocher J, Tomkins S, Turner C, Turnpenny P, Vanderstein A, Vasudevan P, Villard L, Visser L, Wakeling E, Weber A, Williams D, Wilson L, Woods G, Wright M, Writzl K, Yates L.
DOIAbstract
To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling i...
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