Cargando…

Complex Mosaicism of Two Distinct Mutations in a Female Patient With KCNA2-Related Encephalopathy: A Case Report

KCNA2 gene mutations were described to cause a new molecular entity within the developmental and epileptic or epileptic encephalopathies. Here, we firstly reported a patient with an unusual mosaicism for KCNA2, presenting two distinct mosaic missense mutations at the same loci. Clinical trio-based w...

Descripción completa

Detalles Bibliográficos
Autores principales: Gong, Pan, Jiao, Xianru, Zhang, Yuehua, Yang, Zhixian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438874/
https://www.ncbi.nlm.nih.gov/pubmed/32903602
http://dx.doi.org/10.3389/fgene.2020.00911
_version_ 1783572879880749056
author Gong, Pan
Jiao, Xianru
Zhang, Yuehua
Yang, Zhixian
author_facet Gong, Pan
Jiao, Xianru
Zhang, Yuehua
Yang, Zhixian
author_sort Gong, Pan
collection PubMed
description KCNA2 gene mutations were described to cause a new molecular entity within the developmental and epileptic or epileptic encephalopathies. Here, we firstly reported a patient with an unusual mosaicism for KCNA2, presenting two distinct mosaic missense mutations at the same loci. Clinical trio-based whole-exome sequencing using next-generation sequencing (NGS) revealed two novel mutations in KCNA2: c.1225A > T [p.(Ile409Phe)] and c.1225A > C [p.(Ile409Leu)]. Both missense mutations were in mosaic status and Sanger sequencing confirmed them as de novo. The affected 5-year-old girl presented as seizures with fever sensitivity, and mild cognitive and behavioral disorders. EEG showed focal centrotemporal epileptiform discharges accompanied by nocturnal focal seizures at the age of slightly older than 5 years, more likely carrying a loss-of-function mutation of KCNA2-related phenotype. Further NGS with a mean coverage of 6950 × showed 26% (mosaic mutation reads/total reads) of the c.1225A > T mutation and 23% of the c.1225A > C mutation. The sum of their allele fractions was close to 50%, approximately equal to a heterozygous variant. The patient had no seizures for 8 months on combination of levetiracetam (18.75 mg/kg/d) and valproate (20 mg/kg/d) till the last follow-up at the age of 5 years and 11 months. Our findings highlighted the two mosaic mutations responsible for the pathogenesis of KCNA2-related encephalopathy. The patient expanded the mutational spectrum of KCNA2-related encephalopathy and provided new insight into the complex genetic disorder.
format Online
Article
Text
id pubmed-7438874
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-74388742020-09-03 Complex Mosaicism of Two Distinct Mutations in a Female Patient With KCNA2-Related Encephalopathy: A Case Report Gong, Pan Jiao, Xianru Zhang, Yuehua Yang, Zhixian Front Genet Genetics KCNA2 gene mutations were described to cause a new molecular entity within the developmental and epileptic or epileptic encephalopathies. Here, we firstly reported a patient with an unusual mosaicism for KCNA2, presenting two distinct mosaic missense mutations at the same loci. Clinical trio-based whole-exome sequencing using next-generation sequencing (NGS) revealed two novel mutations in KCNA2: c.1225A > T [p.(Ile409Phe)] and c.1225A > C [p.(Ile409Leu)]. Both missense mutations were in mosaic status and Sanger sequencing confirmed them as de novo. The affected 5-year-old girl presented as seizures with fever sensitivity, and mild cognitive and behavioral disorders. EEG showed focal centrotemporal epileptiform discharges accompanied by nocturnal focal seizures at the age of slightly older than 5 years, more likely carrying a loss-of-function mutation of KCNA2-related phenotype. Further NGS with a mean coverage of 6950 × showed 26% (mosaic mutation reads/total reads) of the c.1225A > T mutation and 23% of the c.1225A > C mutation. The sum of their allele fractions was close to 50%, approximately equal to a heterozygous variant. The patient had no seizures for 8 months on combination of levetiracetam (18.75 mg/kg/d) and valproate (20 mg/kg/d) till the last follow-up at the age of 5 years and 11 months. Our findings highlighted the two mosaic mutations responsible for the pathogenesis of KCNA2-related encephalopathy. The patient expanded the mutational spectrum of KCNA2-related encephalopathy and provided new insight into the complex genetic disorder. Frontiers Media S.A. 2020-08-12 /pmc/articles/PMC7438874/ /pubmed/32903602 http://dx.doi.org/10.3389/fgene.2020.00911 Text en Copyright © 2020 Gong, Jiao, Zhang and Yang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Gong, Pan
Jiao, Xianru
Zhang, Yuehua
Yang, Zhixian
Complex Mosaicism of Two Distinct Mutations in a Female Patient With KCNA2-Related Encephalopathy: A Case Report
title Complex Mosaicism of Two Distinct Mutations in a Female Patient With KCNA2-Related Encephalopathy: A Case Report
title_full Complex Mosaicism of Two Distinct Mutations in a Female Patient With KCNA2-Related Encephalopathy: A Case Report
title_fullStr Complex Mosaicism of Two Distinct Mutations in a Female Patient With KCNA2-Related Encephalopathy: A Case Report
title_full_unstemmed Complex Mosaicism of Two Distinct Mutations in a Female Patient With KCNA2-Related Encephalopathy: A Case Report
title_short Complex Mosaicism of Two Distinct Mutations in a Female Patient With KCNA2-Related Encephalopathy: A Case Report
title_sort complex mosaicism of two distinct mutations in a female patient with kcna2-related encephalopathy: a case report
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438874/
https://www.ncbi.nlm.nih.gov/pubmed/32903602
http://dx.doi.org/10.3389/fgene.2020.00911
work_keys_str_mv AT gongpan complexmosaicismoftwodistinctmutationsinafemalepatientwithkcna2relatedencephalopathyacasereport
AT jiaoxianru complexmosaicismoftwodistinctmutationsinafemalepatientwithkcna2relatedencephalopathyacasereport
AT zhangyuehua complexmosaicismoftwodistinctmutationsinafemalepatientwithkcna2relatedencephalopathyacasereport
AT yangzhixian complexmosaicismoftwodistinctmutationsinafemalepatientwithkcna2relatedencephalopathyacasereport