Further delineation of the female phenotype with KDM5C disease causing variants: 19 new individuals and review of the literature

Carmignac V, Nambot S, Lehalle D, Callier P, Moortgat S, Benoit V, Ghoumid J, Delobel B, Smol T, Thuillier C, Zordan C, Naudion S, Bienvenu T, Touraine R, Ramond F, Zweier C, Reis A, Kraus C, Nizon M, Cogne B, Verloes A, Tran Mau-Them F, Sorlin A, Jouan T, Duffourd Y, Tisserant E, Philippe C, Vitobello A, Thevenon J, Faivre L, Thauvin-Robinet C (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Clinical Genetics Wiley-Blackwell

DOI: 10.1111/cge.13755

Abstract

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.

Authors with CRIS profile

Christiane Zweier Medizinische Fakultät André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Cornelia Kraus Institute of Human Genetics

Involved external institutions

Université Bourgogne Franche-Comté FR France (FR) Centre hospitalier universitaire (CHU) de Dijon Bourgogne FR France (FR) Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU) FR France (FR) Hôpital Universitaire Robert-Debré FR France (FR) Institute of Pathology and Genetics (IPG) / Institut de Génétique et de Pathologie BE Belgium (BE) Centre Hospitalier Régional Universitaire de Lille (CHRU de Lille) FR France (FR) Hôpital Saint Vincent de Paul FR France (FR) LILLE 1 University - Science and Technology FR France (FR) Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux FR France (FR) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) FR France (FR) Centre Hospitalier Universitaire de Saint-Étienne (CHU) FR France (FR)

How to cite

APA:

Carmignac, V., Nambot, S., Lehalle, D., Callier, P., Moortgat, S., Benoit, V.,... Thauvin-Robinet, C. (2020). Further delineation of the female phenotype with KDM5C disease causing variants: 19 new individuals and review of the literature. Clinical Genetics. https://doi.org/10.1111/cge.13755

MLA:

Carmignac, Virginie, et al. "Further delineation of the female phenotype with KDM5C disease causing variants: 19 new individuals and review of the literature." Clinical Genetics (2020).

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