Patients with KCNH1 -related intellectual disability without distinctive features of Zimmermann-Laband/Temple-Baraitser syndrome
| Autor: | Sandra Whalen, Olivier Patat, Diane Doummar, Giulia Barcia, Boris Keren, Caroline Karsenty, Sandra Kenis, Julien Buratti, Mathilde Nizon, Lionel Arnaud, Stéphanie Valence, Caroline Nava, Marion Aubert Mucca, Gaetan Lesca, Eric LeGuern, Amélie Piton, Sarah Weckhuysen, Laurent Villard, Benjamin Cogné, Cyril Mignot |
|---|---|
| Přispěvatelé: | Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Hypertrichosis
0303 health sciences medicine.medical_specialty Mutation business.industry [SDV]Life Sciences [q-bio] 030305 genetics & heredity Aplasia medicine.disease medicine.disease_cause Dermatology Phenotype 03 medical and health sciences Epilepsy Intellectual disability Genetics medicine Missense mutation Human medicine business Genetics (clinical) 030304 developmental biology Temple Baraitser syndrome |
| Zdroj: | Journal of Medical Genetics Journal of Medical Genetics, BMJ Publishing Group, 2021, pp.jmedgenet-2020-107511. ⟨10.1136/jmedgenet-2020-107511⟩ Journal of Medical Genetics, 2021, pp.jmedgenet-2020-107511. ⟨10.1136/jmedgenet-2020-107511⟩ Journal of medical genetics |
| ISSN: | 0022-2593 1468-6244 |
| DOI: | 10.1136/jmedgenet-2020-107511⟩ |
| Popis: | De novo missense variants in KCNH1 encoding Kv10.1 are responsible for two clinically recognisable phenotypes: Temple-Baraitser syndrome (TBS) and Zimmermann-Laband syndrome (ZLS). The clinical overlap between these two syndromes suggests that they belong to a spectrum of KCNH1-related encephalopathies. Affected patients have severe intellectual disability (ID) with or without epilepsy, hypertrichosis and distinctive features such as gingival hyperplasia and nail hypoplasia/aplasia (present in 20/23 reported cases).We report a series of seven patients with ID and de novo pathogenic KCNH1 variants identified by whole-exome sequencing or an epilepsy gene panel in whom the diagnosis of TBS/ZLS had not been first considered. Four of these variants, p.(Thr294Met), p.(Ala492Asp), p.(Thr493Asn) and p.(Gly496Arg), were located in the transmembrane domains S3 and S6 of Kv10.1 and one, p.(Arg693Gln), in its C-terminal cyclic nucleotide-binding homology domain (CNBHD). Clinical reappraisal by the referring clinical geneticists confirmed the absence of the distinctive gingival and nail features of TBS/ZLS.Our study expands the phenotypical spectrum of KCNH1-related encephalopathies to individuals with an attenuated extraneurological phenotype preventing a clinical diagnosis of TBS or ZLS. This subtype may be related to recurrent substitutions of the Gly496, suggesting a genotype–phenotype correlation and, possibly, to variants in the CNBHD domain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|