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A de novo missense mutation in SLC12A5 found in a compound heterozygote patient with epilepsy of infancy with migrating focal seizures
Author(s) -
Saito T.,
Ishii A.,
Sugai K.,
Sasaki M.,
Hirose S.
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13049
Subject(s) - compound heterozygosity , epilepsy , missense mutation , genetics , exome sequencing , consanguinity , mutation , biology , west syndrome , genetic heterogeneity , gene , exome , global developmental delay , phenotype , neuroscience
Epilepsy of infancy with migrating focal seizures ( EIMFS ) is an infantile epileptic encephalopathy characterized by refractory seizures, severe psychomotor delay, and multiple moving epileptic discharges. The genetic etiology of EIMFS is relatively homogeneous with the majority of causative mutations found in KCNT1 . Currently, gene panel or whole‐exome sequencing is used for testing. To verify the pathogenicity of a variant, co‐segregation of the variant and the disorder in a pedigree is important; hence, de novo mutations that are judged to be deleterious may be considered pathogenic because the patients are isolated. In contrast, in cases from non‐consanguineous families, genes that cause disorders in a recessive manner should remain as potential candidates. Herein, we performed gene panel sequencing of a patient with EIMFS from a non‐consanguineous family, and found a compound heterozygous constellation consisting of a maternally inherited p. Ser399Leu and a de novo p. Arg880Leu in SLC12A5 , which encodes the neuronal KCC2 cotransporter. These unique mutations show gene variants that act in a recessive manner may be pathogenic for patients from non‐consanguineous families.