Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jan;41(1):69-80.
doi: 10.1002/humu.23915. Epub 2019 Oct 4.

Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature

Claire Bar  1   2   3 , Giulia Barcia  2   3   4 , Mélanie Jennesson  5 , Gwenaël Le Guyader  6   7 , Amy Schneider  8 , Cyril Mignot  9   10 , Gaetan Lesca  11   12 , Delphine Breuillard  1 , Martino Montomoli  13 , Boris Keren  10 , Diane Doummar  14 , Thierry Billette de Villemeur  14 , Alexandra Afenjar  15 , Isabelle Marey  10 , Marion Gerard  16 , Hervé Isnard  17 , Alice Poisson  18 , Sophie Dupont  9   19 , Patrick Berquin  20 , Pierre Meyer  21   22 , David Genevieve  23 , Anne De Saint Martin  24 , Salima El Chehadeh  25 , Jamel Chelly  25 , Agnès Guët  26 , Emmanuel Scalais  27 , Nathalie Dorison  28 , Candace T Myers  29 , Heather C Mefford  30 , Katherine B Howell  31   32 , Carla Marini  13 , Jeremy L Freeman  31   32 , Anca Nica  33 , Gaetano Terrone  34 , Tayeb Sekhara  35 , Anne-Sophie Lebre  36 , Sylvie Odent  37   38 , Lynette G Sadleir  39 , Arnold Munnich  3   4 , Renzo Guerrini  13 , Ingrid E Scheffer  8   31   40 , Edor Kabashi  2   3 , Rima Nabbout  1   2   3
Affiliations
Free article
Review

Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature

Claire Bar et al. Hum Mutat. 2020 Jan.
Free article

Abstract

Developmental and epileptic encephalopathies (DEE) refer to a heterogeneous group of devastating neurodevelopmental disorders. Variants in KCNB1 have been recently reported in patients with early-onset DEE. KCNB1 encodes the α subunit of the delayed rectifier voltage-dependent potassium channel Kv 2.1. We review the 37 previously reported patients carrying 29 distinct KCNB1 variants and significantly expand the mutational spectrum describing 18 novel variants from 27 unreported patients. Most variants occur de novo and mainly consist of missense variants located on the voltage sensor and the pore domain of Kv 2.1. We also report the first inherited variant (p.Arg583*). KCNB1-related encephalopathies encompass a wide spectrum of neurodevelopmental disorders with predominant language difficulties and behavioral impairment. Eighty-five percent of patients developed epilepsies with variable syndromes and prognosis. Truncating variants in the C-terminal domain are associated with a less-severe epileptic phenotype. Overall, this report provides an up-to-date review of the mutational and clinical spectrum of KCNB1, strengthening its place as a causal gene in DEEs and emphasizing the need for further functional studies to unravel the underlying mechanisms.

Keywords: KCNB1; developmental and epileptic encephalopathy; epilepsy; potassium channel.

PubMed Disclaimer

References

Substances