Attenzione: i dati modificati non sono ancora stati salvati. Per confermare inserimenti o cancellazioni di voci è necessario confermare con il tasto SALVA/INSERISCI in fondo alla pagina
IRIS
We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
O'Donnell-Luria, A.H., Pais, L.S., Faundes, V., Wood, J.C., Sveden, A., Luria, V., et al. (2019). Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy. AMERICAN JOURNAL OF HUMAN GENETICS, 104(6), 1210-1222 [10.1016/j.ajhg.2019.03.021].
Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy
O'Donnell-Luria A. H.;Pais L. S.;Faundes V.;Wood J. C.;Sveden A.;Luria V.;Abou Jamra R.;Accogli A.;Amburgey K.;Anderlid B. M.;Azzarello-Burri S.;Basinger A. A.;Bianchini C.;Bird L. M.;Buchert R.;Carre W.;Ceulemans S.;Charles P.;Cox H.;Culliton L.;Curro A.;McRae J. F.;Clayton S.;Fitzgerald T. W.;Kaplanis J.;Prigmore E.;Rajan D.;Sifrim A.;Aitken S.;Akawi N.;Alvi M.;Ambridge K.;Barrett D. M.;Bayzetinova T.;Jones P.;Jones W. D.;King D.;Krishnappa N.;Mason L. E.;Singh T.;Tivey A. R.;Ahmed M.;Anjum U.;Archer H.;Armstrong R.;Awada J.;Balasubramanian M.;Banka S.;Baralle D.;Barnicoat A.;Batstone P.;Baty D.;Bennett C.;Berg J.;Bernhard B.;Bevan A. P.;Bitner-Glindzicz M.;Blair E.;Blyth M.;Bohanna D.;Bourdon L.;Bourn D.;Bradley L.;Brady A.;Brent S.;Brewer C.;Brunstrom K.;Bunyan D. J.;Burn J.;Canham N.;Castle B.;Chandler K.;Chatzimichali E.;Cilliers D.;Clarke A.;Clasper S.;Clayton-Smith J.;Clowes V.;Coates A.;Cole T.;Colgiu I.;Collins A.;Collinson M. N.;Connell F.;Cooper N.;Cresswell L.;Cross G.;Crow Y.;D'Alessandro M.;Dabir T.;Davidson R.;Davies S.;de Vries D.;Dean J.;Deshpande C.;Devlin G.;Dixit A.;Dobbie A.;Donaldson A.;Donnai D.;Donnelly D.;Donnelly C.;Douglas A.;Douzgou S.;Duncan A.;Eason J.;Ellard S.;Ellis I.;Elmslie F.;Evans K.;Everest S.;Fendick T.;Fisher R.;Flinter F.;Foulds N.;Fry A.;Fryer A.;Gardiner C.;Gaunt L.;Ghali N.;Gibbons R.;Gill H.;Goodship J.;Goudie D.;Gray E.;Green A.;Greene P.;Greenhalgh L.;Gribble S.;Harrison R.;Harrison L.;Harrison V.;Hawkins R.;He L.;Hellens S.;Henderson A.;Hewitt S.;Hildyard L.;Hobson E.;Holden S.;Holder M.;Holder S.;Hollingsworth G.;Homfray T.;Humphreys M.;Hurst J.;Hutton B.;Ingram S.;Irving M.;Islam L.;Jackson A.;Jarvis J.;Jenkins L.;Johnson D.;Jones E.;Josifova D.;Joss S.;Kaemba B.;Kazembe S.;Kelsell R.;Kerr B.;Kingston H.;Kini U.;Kinning E.;Kirby G.;Kirk C.;Kivuva E.;Kraus A.;Kumar D.;Kumar V. K. A.;Lachlan K.;Lam W.;Lampe A.;Langman C.;Lees M.;Lim D.;Longman C.;Lowther G.;Lynch S. A.;Magee A.;Maher E.;Male A.;Mansour S.;Marks K.;Martin K.;Maye U.;McCann E.;McConnell V.;McEntagart M.;McGowan R.;McKay K.;McKee S.;McMullan D. J.;McNerlan S.;McWilliam C.;Mehta S.;Metcalfe K.;Middleton A.;Miedzybrodzka Z.;Miles E.;Mohammed S.;Montgomery T.;Moore D.;Morgan S.;Morton J.;Mugalaasi H.;Murday V.;Murphy H.;Naik S.;Nemeth A.;Nevitt L.;Newbury-Ecob R.;Norman A.;O'Shea R.;Ogilvie C.;Ong K. -R.;Park S. -M.;Parker M. J.;Patel C.;Paterson J.;Payne S.;Perrett D.;Phipps J.;Pilz D. T.;Pollard M.;Pottinger C.;Poulton J.;Pratt N.;Prescott K.;Price S.;Pridham A.;Procter A.;Purnell H.;Quarrell O.;Ragge N.;Rahbari R.;Randall J.;Rankin J.;Raymond L.;Rice D.;Robert L.;Roberts E.;Roberts J.;Roberts P.;Roberts G.;Ross A.;Rosser E.;Saggar A.;Samant S.;Sampson J.;Sandford R.;Sarkar A.;Schweiger S.;Scott R.;Scurr I.;Selby A.;Seller A.;Sequeira C.;Shannon N.;Sharif S.;Shaw-Smith C.;Shearing E.;Shears D.;Sheridan E.;Simonic I.;Singzon R.;Skitt Z.;Smith A.;Smith K.;Smithson S.;Sneddon L.;Splitt M.;Squires M.;Stewart F.;Stewart H.;Straub V.;Suri M.;Sutton V.;Swaminathan G. J.;Sweeney E.;Tatton-Brown K.;Taylor C.;Taylor R.;Tein M.;Temple I. K.;Thomson J.;Tischkowitz M.;Tomkins S.;Torokwa A.;Treacy B.;Turner C.;Turnpenny P.;Tysoe C.;Vandersteen A.;Varghese V.;Vasudevan P.;Vijayarangakannan P.;Vogt J.;Wakeling E.;Wallwark S.;Waters J.;Weber A.;Wellesley D.;Whiteford M.;Widaa S.;Wilcox S.;Wilkinson E.;Williams D.;Williams N.;Wilson L.;Woods G.;Wragg C.;Wright M.;Yates L.;Yau M.;Nellaker C.;Parker M.;Firth H. V.;Wright C. F.;FitzPatrick D. R.;Barrett J. C.;Hurles M. E.;Demurger F.;Dowling J. J.;Duban-Bedu B.;Dubourg C.;Eiset S. E.;Escobar L. F.;Ferrarini A.;Haack T. B.;Hashim M.;Heide S.;Helbig K. L.;Helbig I.;Heredia R.;Heron D.;Isidor B.;Jonasson A. R.;Joset P.;Keren B.;Kok F.;Kroes H. Y.;Lavillaureix A.;Lu X.;Maas S. M.;Maegawa G. H. B.;Marcelis C. L. M.;Mark P. R.;Masruha M. R.;McLaughlin H. M.;McWalter K.;Melchinger E. U.;Mercimek-Andrews S.;Nava C.;Pendziwiat M.;Person R.;Ramelli G. P.;Ramos L. L. P.;Rauch A.;Reavey C.;Renieri A.;Riess A.;Sanchez-Valle A.;Sattar S.;Saunders C.;Schwarz N.;Smol T.;Srour M.;Steindl K.;Syrbe S.;Taylor J. C.;Telegrafi A.;Thiffault I.;Trauner D. A.;van der Linden H.;van Koningsbruggen S.;Villard L.;Vogel I.;Weber Y. G.;Wentzensen I. M.;Widjaja E.;Zak J.;Baxter S.;Rodan L. H.
2019-01-01
Abstract
We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
O'Donnell-Luria, A.H., Pais, L.S., Faundes, V., Wood, J.C., Sveden, A., Luria, V., et al. (2019). Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy. AMERICAN JOURNAL OF HUMAN GENETICS, 104(6), 1210-1222 [10.1016/j.ajhg.2019.03.021].
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1126831
Attenzione
Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo
Conferma cancellazione
Sei sicuro che questo prodotto debba essere cancellato?
simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
