Large-scale discovery of novel genetic causes of developmental disorders.
Deciphering Developmental Disorders Study.
Nature
519 :
2015
223-228
661
Absence of heterozygosity due to template switching during replicative rearrangements.
Carvalho CM, Pfundt R, King DA, Lindsay SJ, Zuccherato LW, Macville MV, Liu P, Johnson D, Stankiewicz P, Brown CW, DDD Study, Shaw CA, Hurles ME, Ira G, Hastings PJ, Brunner HG, Lupski JR.
Am J Hum Genet
96 :
2015
555-564
36
B56δ-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.
Houge G, Haesen D, Vissers LE, Mehta S, Parker MJ, Wright M, Vogt J, McKee S, Tolmie JL, Cordeiro N, Kleefstra T, Willemsen MH, Reijnders MR, Berland S, Hayman E, Lahat E, Brilstra EH, van Gassen KL, Zonneveld-Huijssoon E, de Bie CI, Hoischen A, Eichler EE, Holdhus R, Steen VM, Døskeland SO, Hurles ME, FitzPatrick DR, Janssens V.
J Clin Invest
125 :
2015
3051-3062
63
Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.
Akawi N, McRae J, Ansari M, Balasubramanian M, Blyth M, Brady AF, Clayton S, Cole T, Deshpande C, Fitzgerald TW, Foulds N, Francis R, Gabriel G, Gerety SS, Goodship J, Hobson E, Jones WD, Joss S, King D, Klena N, Kumar A, Lees M, Lelliott C, Lord J, McMullan D, O'Regan M, Osio D, Piombo V, Prigmore E, Rajan D, Rosser E, Sifrim A, Smith A, Swaminathan GJ, Turnpenny P, Whitworth J, Wright CF, Firth HV, Barrett JC, Lo CW, FitzPatrick DR, Hurles ME, DDD study.
Nat Genet
47 :
2015
1363-1369
97
Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders.
Singh T, Kurki MI, Curtis D, Purcell SM, Crooks L, McRae J, Suvisaari J, Chheda H, Blackwood D, Breen G, Pietiläinen O, Gerety SS, Ayub M, Blyth M, Cole T, Collier D, Coomber EL, Craddock N, Daly MJ, Danesh J, DiForti M, Foster A, Freimer NB, Geschwind D, Johnstone M, Joss S, Kirov G, Körkkö J, Kuismin O, Holmans P, Hultman CM, Iyegbe C, Lönnqvist J, Männikkö M, McCarroll SA, McGuffin P, McIntosh AM, McQuillin A, Moilanen JS, Moore C, Murray RM, Newbury-Ecob R, Ouwehand W, Paunio T, Prigmore E, Rees E, Roberts D, Sambrook J, Sklar P, St Clair D, Veijola J, Walters JT, Williams H, Swedish Schizophrenia Study, INTERVAL Study, DDD Study, UK10 K Consortium, Sullivan PF, Hurles ME, O'Donovan MC, Palotie A, Owen MJ, Barrett JC.
Nat Neurosci
19 :
2016
571-577
249
BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription.
Dias C, Estruch SB, Graham SA, McRae J, Sawiak SJ, Hurst JA, Joss SK, Holder SE, Morton JE, Turner C, Thevenon J, Mellul K, Sánchez-Andrade G, Ibarra-Soria X, Deriziotis P, Santos RF, Lee SC, Faivre L, Kleefstra T, Liu P, Hurles ME, DDD Study, Fisher SE, Logan DW.
Am J Hum Genet
99 :
2016
253-274
90
Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.
Sifrim A, Hitz MP, Wilsdon A, Breckpot J, Turki SH, Thienpont B, McRae J, Fitzgerald TW, Singh T, Swaminathan GJ, Prigmore E, Rajan D, Abdul-Khaliq H, Banka S, Bauer UM, Bentham J, Berger F, Bhattacharya S, Bu'Lock F, Canham N, Colgiu IG, Cosgrove C, Cox H, Daehnert I, Daly A, Danesh J, Fryer A, Gewillig M, Hobson E, Hoff K, Homfray T, INTERVAL Study, Kahlert AK, Ketley A, Kramer HH, Lachlan K, Lampe AK, Louw JJ, Manickara AK, Manase D, McCarthy KP, Metcalfe K, Moore C, Newbury-Ecob R, Omer SO, Ouwehand WH, Park SM, Parker MJ, Pickardt T, Pollard MO, Robert L, Roberts DJ, Sambrook J, Setchfield K, Stiller B, Thornborough C, Toka O, Watkins H, Williams D, Wright M, Mital S, Daubeney PE, Keavney B, Goodship J, UK10K Consortium, Abu-Sulaiman RM, Klaassen S, Wright CF, Firth HV, Barrett JC, Devriendt K, FitzPatrick DR, Brook JD, Deciphering Developmental Disorders Study, Hurles ME.
Nat Genet
48 :
2016
1060-1065
230
Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy.
Muona M, Ishimura R, Laari A, Ichimura Y, Linnankivi T, Keski-Filppula R, Herva R, Rantala H, Paetau A, Pöyhönen M, Obata M, Uemura T, Karhu T, Bizen N, Takebayashi H, McKee S, Parker MJ, Akawi N, McRae J, Hurles ME, DDD Study, Kuismin O, Kurki MI, Anttonen AK, Tanaka K, Palotie A, Waguri S, Lehesjoki AE, Komatsu M.
Am J Hum Genet
99 :
2016
683-694
53
Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia.
Broix L, Jagline H, Ivanova E, Schmucker S, Drouot N, Clayton-Smith J, Pagnamenta AT, Metcalfe KA, Isidor B, Louvier UW, Poduri A, Taylor JC, Tilly P, Poirier K, Saillour Y, Lebrun N, Stemmelen T, Rudolf G, Muraca G, Saintpierre B, Elmorjani A, Deciphering Developmental Disorders study, Moïse M, Weirauch NB, Guerrini R, Boland A, Olaso R, Masson C, Tripathy R, Keays D, Beldjord C, Nguyen L, Godin J, Kini U, Nischké P, Deleuze JF, Bahi-Buisson N, Sumara I, Hinckelmann MV, Chelly J.
Nat Genet
48 :
2016
1349-1358
60
Prevalence and architecture of de novo mutations in developmental disorders.
Deciphering Developmental Disorders Study.
Nature
542 :
2017
433-438
758
Analysis of exome data for 4293 trios suggests GPI-anchor biogenesis defects are a rare cause of developmental disorders.
Pagnamenta AT, Murakami Y, Taylor JM, Anzilotti C, Howard MF, Miller V, Johnson DS, Tadros S, Mansour S, Temple IK, Firth R, Rosser E, Harrison RE, Kerr B, Popitsch N, DDD Study, Kinoshita T, Taylor JC, Kini U.
Eur J Hum Genet
25 :
2017
669-679
45
Detection of structural mosaicism from targeted and whole-genome sequencing data.
King DA, Sifrim A, Fitzgerald TW, Rahbari R, Hobson E, Homfray T, Mansour S, Mehta SG, Shehla M, Tomkins SE, Vasudevan PC, Hurles ME, Deciphering Developmental Disorders Study.
Genome Res
27 :
2017
1704-1714
35
De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability.
Küry S, van Woerden GM, Besnard T, Proietti Onori M, Latypova X, Towne MC, Cho MT, Prescott TE, Ploeg MA, Sanders S, Stessman HAF, Pujol A, Distel B, Robak LA, Bernstein JA, Denommé-Pichon AS, Lesca G, Sellars EA, Berg J, Carré W, Busk ØL, van Bon BWM, Waugh JL, Deardorff M, Hoganson GE, Bosanko KB, Johnson DS, Dabir T, Holla ØL, Sarkar A, Tveten K, de Bellescize J, Braathen GJ, Terhal PA, Grange DK, van Haeringen A, Lam C, Mirzaa G, Burton J, Bhoj EJ, Douglas J, Santani AB, Nesbitt AI, Helbig KL, Andrews MV, Begtrup A, Tang S, van Gassen KLI, Juusola J, Foss K, Enns GM, Moog U, Hinderhofer K, Paramasivam N, Lincoln S, Kusako BH, Lindenbaum P, Charpentier E, Nowak CB, Cherot E, Simonet T, Ruivenkamp CAL, Hahn S, Brownstein CA, Xia F, Schmitt S, Deb W, Bonneau D, Nizon M, Quinquis D, Chelly J, Rudolf G, Sanlaville D, Parent P, Gilbert-Dussardier B, Toutain A, Sutton VR, Thies J, Peart-Vissers LELM, Boisseau P, Vincent M, Grabrucker AM, Dubourg C, Undiagnosed Diseases Network, Tan WH, Verbeek NE, Granzow M, Santen GWE, Shendure J, Isidor B, Pasquier L, Redon R, Yang Y, State MW, Kleefstra T, Cogné B, GEM HUGO, Deciphering Developmental Disorders Study, Petrovski S, Retterer K, Eichler EE, Rosenfeld JA, Agrawal PB, Bézieau S, Odent S, Elgersma Y, Mercier S.
Am J Hum Genet
101 :
2017
768-788
84
BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange-like syndrome.
Olley G, Ansari M, Bengani H, Grimes GR, Rhodes J, von Kriegsheim A, Blatnik A, Stewart FJ, Wakeling E, Carroll N, Ross A, Park SM, Deciphering Developmental Disorders Study, Bickmore WA, Pradeepa MM, FitzPatrick DR.
Nat Genet
50 :
2018
329-332
71
De novo mutations in regulatory elements in neurodevelopmental disorders.
Short PJ, McRae JF, Gallone G, Sifrim A, Won H, Geschwind DH, Wright CF, Firth HV, FitzPatrick DR, Barrett JC, Hurles ME.
Nature
555 :
2018
611-616
134
Common genetic variants contribute to risk of rare severe neurodevelopmental disorders.
Niemi MEK, Martin HC, Rice DL, Gallone G, Gordon S, Kelemen M, McAloney K, McRae J, Radford EJ, Yu S, Gecz J, Martin NG, Wright CF, Fitzpatrick DR, Firth HV, Hurles ME, Barrett JC.
Nature
562 :
2018
268-271
160
Quantifying the contribution of recessive coding variation to developmental disorders.
Martin HC, Jones WD, McIntyre R, Sanchez-Andrade G, Sanderson M, Stephenson JD, Jones CP, Handsaker J, Gallone G, Bruntraeger M, McRae JF, Prigmore E, Short P, Niemi M, Kaplanis J, Radford EJ, Radford EJ, Akawi N, Balasubramanian M, Dean J, Horton R, Hulbert A, Johnson DS, Johnson K, Kumar D, Lynch SA, Mehta SG, Morton J, Parker MJ, Splitt M, Turnpenny PD, Vasudevan PC, Wright M, Bassett A, Gerety SS, Wright CF, FitzPatrick DR, Firth HV, Hurles ME, Barrett JC, Deciphering Developmental Disorders Study.
Science
362 :
2018
1161-1164
96
Pathogenicity and selective constraint on variation near splice sites.
Lord J, Gallone G, Short PJ, McRae JF, Ironfield H, Wynn EH, Gerety SS, He L, Kerr B, Johnson DS, McCann E, Kinning E, Flinter F, Temple IK, Clayton-Smith J, McEntagart M, Lynch SA, Joss S, Douzgou S, Dabir T, Clowes V, McConnell VPM, Lam W, Wright CF, FitzPatrick DR, Firth HV, Barrett JC, Hurles ME, Deciphering Developmental Disorders study.
Genome Res
29 :
2019
159-170
45
Delineation of dominant and recessive forms of LZTR1-associated Noonan syndrome.
Pagnamenta AT, Kaisaki PJ, Bennett F, Burkitt-Wright E, Martin HC, Ferla MP, Taylor JM, Gompertz L, Lahiri N, Tatton-Brown K, Newbury-Ecob R, Henderson A, Joss S, Weber A, Carmichael J, Turnpenny PD, McKee S, Forzano F, Ashraf T, Bradbury K, Shears D, Kini U, de Burca A, DDD Study, Blair E, Taylor JC, Stewart H.
Clin Genet
95 :
2019
693-703
24
Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP.
Thormann A, Halachev M, McLaren W, Moore DJ, Svinti V, Campbell A, Kerr SM, Tischkowitz M, Hunt SE, Dunlop MG, Hurles ME, Wright CF, Firth HV, Cunningham F, FitzPatrick DR.
Nat Commun
10 :
2019
2373
66
Exome-wide assessment of the functional impact and pathogenicity of multinucleotide mutations.
Kaplanis J, Akawi N, Gallone G, McRae JF, Prigmore E, Wright CF, Fitzpatrick DR, Firth HV, Barrett JC, Hurles ME, Deciphering Developmental Disorders study.
Genome Res
29 :
2019
1047-1056
25
Clinically-relevant postzygotic mosaicism in parents and children with developmental disorders in trio exome sequencing data.
Wright CF, Prigmore E, Rajan D, Handsaker J, McRae J, Kaplanis J, Fitzgerald TW, FitzPatrick DR, Firth HV, Hurles ME.
Nat Commun
10 :
2019
2985
41
AVADA: toward automated pathogenic variant evidence retrieval directly from the full-text literature.
Birgmeier J, Deisseroth CA, Hayward LE, Galhardo LMT, Tierno AP, Jagadeesh KA, Stenson PD, Cooper DN, Bernstein JA, Haeussler M, Bejerano G.
Genet Med
22 :
2020
362-370
14
Contribution of retrotransposition to developmental disorders.
Gardner EJ, Prigmore E, Gallone G, Danecek P, Samocha KE, Handsaker J, Gerety SS, Ironfield H, Short PJ, Sifrim A, Singh T, Chandler KE, Clement E, Lachlan KL, Prescott K, Rosser E, FitzPatrick DR, Firth HV, Hurles ME.
Nat Commun
10 :
2019
4630
35
GTX.Digest.VCF: an online NGS data interpretation system based on intelligent gene ranking and large-scale text mining.
Jiang Y, Wu C, Zhang Y, Zhang S, Yu S, Lei P, Lu Q, Xi Y, Wang H, Song Z.
BMC Med Genomics
12 :
2019
193
4
AMELIE speeds Mendelian diagnosis by matching patient phenotype and genotype to primary literature.
Birgmeier J, Haeussler M, Deisseroth CA, Steinberg EH, Jagadeesh KA, Ratner AJ, Guturu H, Wenger AM, Diekhans ME, Stenson PD, Cooper DN, Ré C, Beggs AH, Bernstein JA, Bejerano G.
Sci Transl Med
12 :
2020
eaau9113
40
SLC12A2 variants cause a neurodevelopmental disorder or cochleovestibular defect.
McNeill A, Iovino E, Mansard L, Vache C, Baux D, Bedoukian E, Cox H, Dean J, Goudie D, Kumar A, Newbury-Ecob R, Fallerini C, Renieri A, Lopergolo D, Mari F, Blanchet C, Willems M, Roux AF, Pippucci T, Delpire E.
Brain
143 :
2020
2380-2387
30
Evidence for 28 genetic disorders discovered by combining healthcare and research data.
Kaplanis J, Samocha KE, Wiel L, Zhang Z, Arvai KJ, Eberhardt RY, Gallone G, Lelieveld SH, Martin HC, McRae JF, Short PJ, Torene RI, de Boer E, Danecek P, Gardner EJ, Huang N, Lord J, Martincorena I, Pfundt R, Reijnders MRF, Yeung A, Yntema HG, Deciphering Developmental Disorders Study, Vissers LELM, Juusola J, Wright CF, Brunner HG, Firth HV, FitzPatrick DR, Barrett JC, Hurles ME, Gilissen C, Retterer K.
Nature
586 :
2020
757-762
253
Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy.
Fry AE, Marra C, Derrick AV, Pickrell WO, Higgins AT, Te Water Naude J, McClatchey MA, Davies SJ, Metcalfe KA, Tan HJ, Mohanraj R, Avula S, Williams D, Brady LI, Mesterman R, Tarnopolsky MA, Zhang Y, Yang Y, Wang X, Genomics England Research Consortium, Rees MI, Goldfarb M, Chung SK.
Am J Hum Genet
108 :
2021
176-185
12
The contribution of X-linked coding variation to severe developmental disorders.
Martin HC, Gardner EJ, Samocha KE, Kaplanis J, Akawi N, Sifrim A, Eberhardt RY, Tavares ALT, Neville MDC, Niemi MEK, Gallone G, McRae J, Deciphering Developmental Disorders Study, Wright CF, FitzPatrick DR, Firth HV, Hurles ME.
Nat Commun
12 :
2021
627
25
Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms.
Wright CF, Quaife NM, Ramos-Hernández L, Danecek P, Ferla MP, Samocha KE, Kaplanis J, Gardner EJ, Eberhardt RY, Chao KR, Karczewski KJ, Morales J, Gallone G, Balasubramanian M, Banka S, Gompertz L, Kerr B, Kirby A, Lynch SA, Morton JEV, Pinz H, Sansbury FH, Stewart H, Zuccarelli BD, Genomics England Research Consortium, Cook SA, Taylor JC, Juusola J, Retterer K, Firth HV, Hurles ME, Lara-Pezzi E, Barton PJR, Whiffin N.
Am J Hum Genet
108 :
2021
1083-1094
32
Detecting cryptic clinically relevant structural variation in exome-sequencing data increases diagnostic yield for developmental disorders.
Gardner EJ, Sifrim A, Lindsay SJ, Prigmore E, Rajan D, Danecek P, Gallone G, Eberhardt RY, Martin HC, Wright CF, FitzPatrick DR, Firth HV, Hurles ME.
Am J Hum Genet
108 :
2021
2186-2194
11
Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases.
Yuan X, Wang J, Dai B, Sun Y, Zhang K, Chen F, Peng Q, Huang Y, Zhang X, Chen J, Xu X, Chuan J, Mu W, Li H, Fang P, Gong Q, Zhang P.
Brief Bioinform
23 :
2022
bbac019
20
Genetic and chemotherapeutic influences on germline hypermutation.
Kaplanis J, Ide B, Sanghvi R, Neville M, Danecek P, Coorens T, Prigmore E, Short P, Gallone G, McRae J, Genomics England Research Consortium, Carmichael J, Barnicoat A, Firth H, O'Brien P, Rahbari R, Hurles M.
Nature
605 :
2022
503-508
43
X-CAP improves pathogenicity prediction of stopgain variants.
Rastogi R, Stenson PD, Cooper DN, Bejerano G.
Genome Med
14 :
2022
81
2
Integrated gene analyses of de novo variants from 46,612 trios with autism and developmental disorders.
Wang T, Kim CN, Bakken TE, Gillentine MA, Henning B, Mao Y, Gilissen C, SPARK Consortium, Nowakowski TJ, Eichler EE.
Proc Natl Acad Sci U S A
119 :
2022
e2203491119
27
IMPROVE-DD: Integrating multiple phenotype resources optimizes variant evaluation in genetically determined developmental disorders.
Aitken S, Firth HV, Wright CF, Hurles ME, FitzPatrick DR, Semple CA.
HGG Adv
4 :
2023
100162
2
Hypothesis-free phenotype prediction within a genetics-first framework.
Lu C, Zaucha J, Gam R, Fang H, Ben Smithers, Oates ME, Bernabe-Rubio M, Williams J, Zelenka N, Pandurangan AP, Tandon H, Shihab H, Kalaivani R, Sung M, Sardar AJ, Tzovoras BG, Danovi D, Gough J.
Nat Commun
14 :
2023
919
2
Evaluation of in silico pathogenicity prediction tools for the classification of small in-frame indels.
Cannon S, Williams M, Gunning AC, Wright CF.
BMC Med Genomics
16 :
2023
36
3
Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland.
Wright CF, Campbell P, Eberhardt RY, Aitken S, Perrett D, Brent S, Danecek P, Gardner EJ, Chundru VK, Lindsay SJ, Andrews K, Hampstead J, Kaplanis J, Samocha KE, Middleton A, Foreman J, Hobson RJ, Parker MJ, Martin HC, FitzPatrick DR, Hurles ME, Firth HV, DDD Study.
N Engl J Med
388 :
2023
1559-1571
54
Sex difference contributes to phenotypic diversity in individuals with neurodevelopmental disorders.
Cuppens T, Shatto J, Mangnier L, Kumar AA, Ng AC, Kaur M, Bui TA, Leclercq M, Droit A, Dunham I, Bolduc FV.
Front Pediatr
11 :
2023
1172154
0
Developing a cluster-based approach for deciphering complexity in individuals with neurodevelopmental differences.
Cuppens T, Kaur M, Kumar AA, Shatto J, Ng AC, Leclercq M, Reformat MZ, Droit A, Dunham I, Bolduc FV.
Front Pediatr
11 :
2023
1171920
0
Refined preferences of prioritizers improve intelligent diagnosis for Mendelian diseases.
Yuan X, Su J, Wang J, Dai B, Sun Y, Zhang K, Li Y, Chuan J, Tang C, Yu Y, Gong Q.
Sci Rep
14 :
2024
2845
0
Investigating the role of common cis-regulatory variants in modifying penetrance of putatively damaging, inherited variants in severe neurodevelopmental disorders.
Wigdor EM, Samocha KE, Eberhardt RY, Chundru VK, Firth HV, Wright CF, Hurles ME, Martin HC.
Sci Rep
14 :
2024
8708
2
Complex trait associations in rare diseases and impacts on Mendelian variant interpretation.
Smail C, Ge B, Keever-Keigher MR, Schwendinger-Schreck C, Cheung WA, Johnston JJ, Barrett C, Genomic Answers for Kids Consortium, Feldman K, Cohen ASA, Farrow EG, Thiffault I, Grundberg E, Pastinen T.
Nat Commun
15 :
2024
8196
0
Federated analysis of autosomal recessive coding variants in 29,745 developmental disorder patients from diverse populations.
Chundru VK, Zhang Z, Walter K, Lindsay SJ, Danecek P, Eberhardt RY, Gardner EJ, Malawsky DS, Wigdor EM, Torene R, Retterer K, Wright CF, Ólafsdóttir H, Guillen Sacoto MJ, Ayaz A, Akbeyaz IH, Türkdoğan D, Al Balushi AI, Bertoli-Avella A, Bauer P, Szenker-Ravi E, Reversade B, McWalter K, Sheridan E, Firth HV, Hurles ME, Samocha KE, Ustach VD, Martin HC.
Nat Genet
56 :
2024
2046-2053
2