Portal de investigación
Rare pathogenic variants in WNK3 cause X-linked intellectual disability.
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Kury, Sebastien
- Zhang, Jinwei
- Besnard, Thomas
- Zeng, Xue
- Robert, Stephanie M.
- Josiah, Sunday S.
- Kiziltug, Emre
- Denomme-Pichon, Anne-Sophie
- Cogne, Benjamin
- Kundishora, Adam J.
- Hao, Le T.
- Li, Hong
- Stevenson, Roger E.
- Louie, Raymond J.
- Deb, Wallid
- Torti, Erin
- Vignard, Virginie
- McWalter, Kirsty
- Raymond, F. Lucy
- Rajabi, Farrah
- Ranza, Emmanuelle
- Grozeva, Detelina
- Coury, Stephanie A.
- Blanc, Xavier
- Brischoux-Boucher, Elise
- Keren, Boris
- Ounap, Katrin
- Reinson, Karit
- Ilves, Pilvi
- Wentzensen, Ingrid M.
- Barr, Eileen E.
- Guihard, Solveig Heide
- Charles, Perrine
- Seaby, Eleanor G.
- Monaghan, Kristin G.
- Rio, Marlene
- van Bever, Yolande
- van Slegtenhorst, Marjon
- Chung, Wendy K.
- Wilson, Ashley
- Quinquis, Delphine
- Breheret, Flora
- Retterer, Kyle
- Lindenbaum, Pierre
- Scalais, Emmanuel
- Rhodes, Lindsay
- Stouffs, Katrien
- Pereira, Elaine M.
- Berger, Sara M.
- Milla, Sarah S.
- Jaykumar, Ankita B.
- Cobb, Melanie H.
- Panchagnula, Shreyas
- Duy, Phan Q.
- Vincent, Marie
- Mercier, Sandra
- Gilbert-Dussardier, Brigitte
- Le Guillou, Xavier
- Audebert-Bellanger, Severine
- Odent, Sylvie
- Schmitt, Sebastien
- Boisseau, Pierre
- Bonneau, Dominique
- Toutain, Annick
- Colin, Estelle
- Pasquier, Laurent
- Redon, Richard
- Bouman, Arjan
- Rosenfeld, Jill A.
- Friez, Michael J.
- Perez-Pena, Helena
- Akhtar Rizvi, Syed Raza
- Haider, Shozeb
- Antonarakis, Stylianos E.
- Schwartz, Charles E.
- Bezieau, Stephane
- Kahle, Kristopher T.
- Isidor, Bertrand
Grupos
Abstract
PURPOSE: WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown. METHOD: We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID). RESULTS: We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.Pro204Arg, p.Leu300Ser, p.Glu607Val) in WNK3 in 14 male individuals from 6 unrelated families. Affected individuals had identifier with variable presence of epilepsy and structural brain defects. WNK3 variants cosegregated with the disease in 3 different families with multiple affected individuals. This included 1 large family previously diagnosed with X-linked Prieto syndrome. WNK3 pathogenic missense variants localize to the catalytic domain and impede the inhibitory phosphorylation of the neuronal-specific chloride cotransporter KCC2 at threonine 1007, a site critically regulated during the development of synaptic inhibition. CONCLUSION: Pathogenic WNK3 variants cause a rare form of human X-linked identifier with variable epilepsy and structural brain abnormalities and implicate impaired phospho-regulation of KCC2 as a pathogenic mechanism.
Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
Datos de la publicación
- ISSN/ISSNe:
- 1098-3600, 1530-0366
- Tipo:
- Article
- Páginas:
- 1941-1951
- Factor de Impacto:
- 2,877 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
GENETICS IN MEDICINE NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 2
Documentos
- No hay documentos
Filiaciones
Keywords
- Exome sequencing; KCC2; Neurodevelopmental disease; WNK3; X-linked intellectual disability
Proyectos asociados
RED DE BIOBANCOS (BIOBANCOS)
RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010
COMPREHENSIVE, INTEGRATIVE AND GENOMIC APPROACH TO THE UNDERSTANDING AND TREATMENT OF CANCER AND LEUKEMIA.
Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO
PIE13/00046 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2014
LA RUTA DE LA OXITOCINA EN LOS TRASTORNOS DEL ESPECTRO AUTISTA: IMPORTANCIA DE LAS VARIANTES GENÉTICAS CON RELEVANCIA FUNCIONAL.
Investigador Principal: CARMEN ORELLANA ALONSO
2014_0056_CRC_ORELLANA . 2014
ABORDAJE GENÓMICO PARA LA IDENTIFICACIÓN DE NUEVOS GENES Y MÓDULOS FUNCIONALES RESPONSABLES DE DISCAPACIDAD INTELECTUAL GRAVE.
Investigador Principal: FRANCISCO MARTÍNEZ CASTELLANO
PI14/00350 . INSTITUTO DE SALUD CARLOS III . 2015
NUEVA APROXIMACIÓN GENÓMICA PARA EL DIAGNÓSTICO DE AUTISMO Y DISCAPACIDAD INTELECTUAL: IMPORTANCIA DE LAS MUTACIONES ADQUIRIDAS EN MOSAICISMO SOMÁTICO Y DE NUEVOS GENES CANDIDATOS.
Investigador Principal: SANDRA MONFORT MEMBRADO
2018_0170_CRC_MUTUA MADRILEÑA_MONFORT . FUNDACION MUTUA MADRILEÑA . 2018
Cita
Kury S,Zhang J,Besnard T,Caro A,Zeng X,Robert SM,Josiah SS,Kiziltug E,Denomme A,Cogne B,Kundishora AJ,Hao L,Li H,Stevenson RE,Louie RJ,Deb W,Torti E,Vignard V,McWalter K,Raymond FL,Rajabi F,Ranza E,Grozeva D,Coury SA,Blanc X,Brischoux E,Keren B,Ounap K,Reinson K,Ilves P,Wentzensen IM,Barr EE,Guihard SH,Charles P,Seaby EG,Monaghan KG,Rio M,van Y,van M,Chung WK,Wilson A,Quinquis D,Breheret F,Retterer K,Lindenbaum P,Scalais E,Rhodes L,Stouffs K,Pereira EM,Berger SM,Milla SS,Jaykumar AB,Cobb MH,Panchagnula S,Duy PQ,Vincent M,Mercier S,Gilbert B,Le X,Audebert S,Odent S,Schmitt S,Boisseau P,Bonneau D,Toutain A,Colin E,Pasquier L,Redon R,Bouman A,Rosenfeld JA,Friez MJ,Perez H,Akhtar SR,Haider S,Antonarakis SE,Schwartz CE,Martinez F,Bezieau S,Kahle KT,Isidor B. Rare pathogenic variants in WNK3 cause X-linked intellectual disability. Genet Med. 2022. 24. (9):p. 1941-1951. IF:8,800. (1).