Further delineation of the female phenotype ...
Document type :
Article dans une revue scientifique: Article de synthèse/Review paper
DOI :
PMID :
Permalink :
Title :
Further delineation of the female phenotype with kdm5c disease causing variants: 19 new individuals and review of the literature
Author(s) :
Carmignac, Virginie [Auteur]
Nambot, Sophie [Auteur]
Lehalle, Daphne [Auteur]
Callier, Patrick [Auteur]
Moortgat, Stephanie [Auteur]
Benoit, Valerie [Auteur]
Ghoumid, Jamal [Auteur]
Maladies RAres du DÉveloppement embryonnaire et du Métabolisme : du phénotype au génotype et à la Fonction (RADEME) - ULR 7364
Delobel, Bruno [Auteur]
Smol, Thomas [Auteur]
Thuillier, Caroline [Auteur]
Zordan, Cecile [Auteur]
Naudion, Sophie [Auteur]
Bienvenu, Thierry [Auteur]
Touraine, Renaud [Auteur]
Ramond, Francis [Auteur]
Zweier, Christiane [Auteur]
Reis, Andre [Auteur]
Kraus, Cornelia [Auteur]
Nizon, Mathilde [Auteur]
Cogne, Benjamin [Auteur]
Verloes, Alain [Auteur]
Tran Mau-Them, Frederic [Auteur]
Sorlin, Arthur [Auteur]
Jouan, Thibaud [Auteur]
Duffourd, Yannis [Auteur]
Tisserant, Emilie [Auteur]
Philippe, Christophe [Auteur]
Vitobello, Antonio [Auteur]
Thevenon, Julien [Auteur]
Faivre, Laurence [Auteur]
Thauvin-Robinet, Christel [Auteur]
Nambot, Sophie [Auteur]
Lehalle, Daphne [Auteur]
Callier, Patrick [Auteur]
Moortgat, Stephanie [Auteur]
Benoit, Valerie [Auteur]
Ghoumid, Jamal [Auteur]
Maladies RAres du DÉveloppement embryonnaire et du Métabolisme : du phénotype au génotype et à la Fonction (RADEME) - ULR 7364
Delobel, Bruno [Auteur]
Smol, Thomas [Auteur]
Thuillier, Caroline [Auteur]
Zordan, Cecile [Auteur]
Naudion, Sophie [Auteur]
Bienvenu, Thierry [Auteur]
Touraine, Renaud [Auteur]
Ramond, Francis [Auteur]
Zweier, Christiane [Auteur]
Reis, Andre [Auteur]
Kraus, Cornelia [Auteur]
Nizon, Mathilde [Auteur]
Cogne, Benjamin [Auteur]
Verloes, Alain [Auteur]
Tran Mau-Them, Frederic [Auteur]
Sorlin, Arthur [Auteur]
Jouan, Thibaud [Auteur]
Duffourd, Yannis [Auteur]
Tisserant, Emilie [Auteur]
Philippe, Christophe [Auteur]
Vitobello, Antonio [Auteur]
Thevenon, Julien [Auteur]
Faivre, Laurence [Auteur]
Thauvin-Robinet, Christel [Auteur]
Journal title :
Clinical Genetics
Abbreviated title :
Clin. Genet.
Volume number :
98
Publication date :
2020-05-29
ISSN :
0009-9163
Keyword(s) :
KDM5C
data-sharing
exome
X-linked intellectual disability
females
data-sharing
exome
X-linked intellectual disability
females
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
X-linked intellectual disability (XLID) is a genetically heterogeneous condition involving more than 100 genes. To date, 35 pathogenic variants have been reported in the lysine specific demethylase 5C (KDM5C) gene. KDM5C ...
Show more >X-linked intellectual disability (XLID) is a genetically heterogeneous condition involving more than 100 genes. To date, 35 pathogenic variants have been reported in the lysine specific demethylase 5C (KDM5C) gene. KDM5C variants are one of the major causes of moderate to severe XLID. Affected males present with short stature, distinctive facial features, behavioral disorders, epilepsy, and spasticity. For most of these variants, related female carriers have been reported, but phenotypic descriptions were poor. Here, we present clinical and molecular features of 19 females carrying 10 novel heterozygous variants affecting KDM5C function, including five probands with de novo variants. Four heterozygous females were asymptomatic. All affected individuals presented with learning disabilities or ID (mostly moderate), and four also had a language impairment mainly affecting expression. Behavioral disturbances were frequent, and endocrine disorders were more frequent in females. In conclusion, our findings provide evidence of the role of KDM5C in ID in females highlighting the increasing implication of XLID genes in females, even in sporadic affected individuals. Disease expression of XLID in females should be taken into consideration for genetic counseling.Show less >
Show more >X-linked intellectual disability (XLID) is a genetically heterogeneous condition involving more than 100 genes. To date, 35 pathogenic variants have been reported in the lysine specific demethylase 5C (KDM5C) gene. KDM5C variants are one of the major causes of moderate to severe XLID. Affected males present with short stature, distinctive facial features, behavioral disorders, epilepsy, and spasticity. For most of these variants, related female carriers have been reported, but phenotypic descriptions were poor. Here, we present clinical and molecular features of 19 females carrying 10 novel heterozygous variants affecting KDM5C function, including five probands with de novo variants. Four heterozygous females were asymptomatic. All affected individuals presented with learning disabilities or ID (mostly moderate), and four also had a language impairment mainly affecting expression. Behavioral disturbances were frequent, and endocrine disorders were more frequent in females. In conclusion, our findings provide evidence of the role of KDM5C in ID in females highlighting the increasing implication of XLID genes in females, even in sporadic affected individuals. Disease expression of XLID in females should be taken into consideration for genetic counseling.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Collections :
Submission date :
2021-09-02T07:02:30Z