The contribution of X-linked coding variation to severe developmental disorders
Creators: name: Martin, Hilary C.
name: Gardner, Eugene J.
name: Samocha, Kaitlin E.
name: Kaplanis, Joanna
name: Akawi, Nadia
name: Sifrim, Alejandro
name: Eberhardt, Ruth Y.
name: Tavares, Ana Lisa Taylor
name: Neville, Matthew D. C.
name: Niemi, Mari E. K.
name: Gallone, Giuseppe
name: McRae, Jeremy
name: Wright, Caroline F.
name: FitzPatrick, David R.
name: Firth, Helen V.
name: Hurles, Matthew E.
name: Borras, Silvia
name: Clark, Caroline
name: Dean, John
name: Miedzybrodzka, Zosia
name: Ross, Alison
name: Tennant, Stephen
name: Dabir, Tabib
name: Donnelly, Deirdre
name: Humphreys, Mervyn
name: Magee, Alex
name: McConnell, Vivienne
name: McKee, Shane
name: McNerlan, Susan
name: Morrison, Patrick J.
name: Rea, Gillian
name: Stewart, Fiona
name: Cole, Trevor
name: Cooper, Nicola
name: Cooper-Charles, Lisa
name: Cox, Helen
name: Islam, Lily
name: Jarvis, Joanna
name: Keelagher, Rebecca
name: Lim, Derek
name: McMullan, Dominic
name: Morton, Jenny
name: Naik, Swati
name: O’Driscoll, Mary
name: Ong, Kai-Ren
name: Osio, Deborah
name: Ragge, Nicola
name: Turton, Sarah
name: Vogt, Julie
name: Williams, Denise
name: Bodek, Simon
name: Donaldson, Alan
name: Hills, Alison
name: Low, Karen
name: Newbury-Ecob, Ruth
name: Norman, Andrew M.
name: Roberts, Eileen
name: Scurr, Ingrid
name: Smithson, Sarah
name: Tooley, Madeleine
name: Abbs, Steve
name: Armstrong, Ruth
name: Dunn, Carolyn
name: Holden, Simon
name: Park, Soo-Mi
name: Paterson, Joan
name: Raymond, Lucy
name: Reid, Evan
name: Sandford, Richard
name: Simonic, Ingrid
name: Tischkowitz, Marc
name: Woods, Geoff
name: Bradley, Lisa
name: Comerford, Joanne
name: Green, Andrew
name: Lynch, Sally
name: McQuaid, Shirley
name: Mullaney, Brendan
name: Berg, Jonathan
name: Goudie, David
name: Mavrak, Eleni
name: McLean, Joanne
name: McWilliam, Catherine
name: Reavey, Eleanor
name: Azam, Tara
name: Cleary, Elaine
name: Jackson, Andrew
name: Lam, Wayne
name: Lampe, Anne
name: Moore, David
name: Porteous, Mary
name: Baple, Emma
name: Baptista, Júlia
name: Brewer, Carole
name: Castle, Bruce
name: Kivuva, Emma
name: Owens, Martina
name: Rankin, Julia
name: Shaw-Smith, Charles
name: Turner, Claire
name: Turnpenny, Peter
name: Tysoe, Carolyn
name: Bradley, Therese
name: Davidson, Rosemarie
name: Gardiner, Carol
name: Joss, Shelagh
name: Kinning, Esther
name: Longman, Cheryl
name: McGowan, Ruth
name: Murday, Victoria
name: Pilz, Daniela
name: Tobias, Edward
name: Whiteford, Margo
name: Williams, Nicola
name: Barnicoat, Angela
name: Clement, Emma
name: Faravelli, Francesca
name: Hurst, Jane
name: Jenkins, Lucy
name: Jones, Wendy
name: Kumar, V.K.Ajith
name: Lees, Melissa
name: Loughlin, Sam
name: Male, Alison
name: Morrogh, Deborah
name: Rosser, Elisabeth
name: Scott, Richard
name: Wilson, Louise
name: Beleza, Ana
name: Deshpande, Charu
name: Flinter, Frances
name: Holder, Muriel
name: Irving, Melita
name: Izatt, Louise
name: Josifova, Dragana
name: Mohammed, Shehla
name: Molenda, Aneta
name: Robert, Leema
name: Roworth, Wendy
name: Ruddy, Deborah
name: Ryten, Mina
name: Yau, Shu
name: Bennett, Christopher
name: Blyth, Moira
name: Campbell, Jennifer
name: Coates, Andrea
name: Dobbie, Angus
name: Hewitt, Sarah
name: Hobson, Emma
name: Jackson, Eilidh
name: Jewell, Rosalyn
name: Kraus, Alison
name: Prescott, Katrina
name: Sheridan, Eamonn
name: Thomson, Jenny
name: Bradshaw, Kirsty
name: Dixit, Abhijit
name: Eason, Jacqueline
name: Haines, Rebecca
name: Harrison, Rachel
name: Mutch, Stacey
name: Sarkar, Ajoy
name: Searle, Claire
name: Shannon, Nora
name: Sharif, Abid
name: Suri, Mohnish
name: Vasudevan, Pradeep
name: Canham, Natalie
name: Ellis, Ian
name: Greenhalgh, Lynn
name: Howard, Emma
name: Stinton, Victoria
name: Swale, Andrew
name: Weber, Astrid
name: Banka, Siddharth
name: Breen, Catherine
name: Briggs, Tracy
name: Burkitt-Wright, Emma
name: Chandler, Kate
name: Clayton-Smith, Jill
name: Donnai, Dian
name: Douzgou, Sofia
name: Gaunt, Lorraine
name: Jones, Elizabeth
name: Kerr, Bronwyn
name: Langley, Claire
name: Metcalfe, Kay
name: Smith, Audrey
name: Wright, Ronnie
name: Bourn, David
name: Burn, John
name: Fisher, Richard
name: Hellens, Steve
name: Henderson, Alex
name: Montgomery, Tara
name: Splitt, Miranda
name: Straub, Volker
name: Wright, Michael
name: Zwolinski, Simon
name: Allen, Zoe
name: Bernhard, Birgitta
name: Brady, Angela
name: Brooks, Claire
name: Busby, Louise
name: Clowes, Virginia
name: Ghali, Neeti
name: Holder, Susan
name: Ibitoye, Rita
name: Wakeling, Emma
name: Blair, Edward
name: Carmichael, Jenny
name: Cilliers, Deirdre
name: Clasper, Susan
name: Gibbons, Richard
name: Kini, Usha
name: Lester, Tracy
name: Nemeth, Andrea
name: Poulton, Joanna
name: Price, Sue
name: Shears, Debbie
name: Stewart, Helen
name: Wilkie, Andrew
name: Albaba, Shadi
name: Baker, Duncan
name: Balasubramanian, Meena
name: Johnson, Diana
name: Parker, Michael
name: Quarrell, Oliver
name: Stewart, Alison
name: Willoughby, Josh
name: Crosby, Charlene
name: Elmslie, Frances
name: Homfray, Tessa
name: Jin, Huilin
name: Lahiri, Nayana
name: Mansour, Sahar
name: Marks, Karen
name: McEntagart, Meriel
name: Saggar, Anand
name: Tatton-Brown, Kate
name: Butler, Rachel
name: Clarke, Angus
name: Corrin, Sian
name: Fry, Andrew
name: Kamath, Arveen
name: McCann, Emma
name: Mugalaasi, Hood
name: Pottinger, Caroline
name: Procter, Annie
name: Sampson, Julian
name: Sansbury, Francis
name: Varghese, Vinod
name: Baralle, Diana
name: Callaway, Alison
name: Cassidy, Emma J.
name: Daniels, Stacey
name: Douglas, Andrew
name: Foulds, Nicola
name: Hunt, David
name: Kharbanda, Mira
name: Lachlan, Katherine
name: Mercer, Catherine
name: Side, Lucy
name: Temple, I. Karen
name: Wellesley, Diana
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021
Subjects: Article
/631/208/205
/631/208/1516
/631/208/366
/49/23
article

description: Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders.