A Japanese family with dystonia due to a pathogenic variant in SGCE

• Published in: Human genome variation Vol. 9; no. 1; p. 29
• Main Authors: Morikawa, Takuya, Miura, Shiroh, Fan, Luoming, Watanabe, Emina, Fujioka, Ryuta, Motooka, Hiromichi, Yasumoto, Shingo, Uchiyama, Yusuke, Shibata, Hiroki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-08-2022; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/208/212/2301; 631/378; Alleles; Biomedical and Life Sciences; Biomedicine; Data Report; Dystonia; Families & family life; Gene Expression; Gene Function; Gene Therapy; Genes; Genomes; Genomics; Human Genetics; Medical research; Medicine; Molecular Medicine; Mutation; Neurological disorders; Neurology; Pathogenicity
• ISSN: 2054-345X; 2054-345X
• DOI: 10.1038/s41439-022-00207-8

Dystonia (DYT) is a heterogeneous neurological disorder, and there are many types of DYT depending on the responsible genes. DYT11 is an autosomal dominant DYT caused by functional variants in the
SGCE
gene. We examined a Japanese patient with myoclonic dystonia. By using exome analysis, we identified a rare variant in the
SGCE
gene, NM_003919.3: c.304C > T [Arg102*], in this patient. Therefore, this patient has been molecularly diagnosed with DYT11. By Sanger sequencing, we confirmed that this variant was paternally inherited in this patient. By allele-specific PCR, we confirmed that the maternally inherited normal allele of
SGCE
was silenced, and only the paternally inherited variant allele was expressed in this patient. Despite the pathogenicity, identical variants have been recurrently reported in eight independent families from different ethnicities, suggesting recurrent mutations at this mutational hotspot in
SGCE
.