期刊
CLINICAL GENETICS
卷 100, 期 6, 页码 743-747出版社
WILEY
DOI: 10.1111/cge.14055
关键词
cerebellar ataxia; dystonia; genetics; KMT2B
资金
- Centro Hospitalar Universitario do Porto
- GenomePT [POCI-01-0145-FEDER-022184]
Hereditary cerebellar ataxias are a group of neurodegenerative disorders affecting the cerebellum and/or cerebellar pathways. Next-generation sequencing has expanded the understanding of genes causing ataxia. The study suggests KMT2B may be involved in hereditary cerebellar ataxias.
Hereditary cerebellar ataxias comprise a heterogeneous group of neurodegenerative disorders affecting the cerebellum and/or cerebellar pathways. Next-generation sequencing techniques have contributed substantially to the expansion of ataxia-causing genes, including genes classically described in alternative phenotypes. Herein, we describe a patient with adult-onset cerebellar ataxia, minor dystonia, neuropathy, seizure and ophthalmological pathology, who bears a novel variant in KMT2B (NM_014727.2:c.3334 + 1G > A). Bioinformatic analysis suggested this variant completely abolished the splice-site at exon 8/intron 8, which was confirmed through analysis of mRNA extracted from fibroblasts. Exon 8 skipping would ultimately translate as an in-frame deletion at the protein level, corresponding to the loss of 91 aminoacids [p.(Gly1020_Asn1111del)]. So far, KMT2B disease causing variants have been described in patients with dystonia or neurodevelopmental delay, with no reports of a cerebellar predominant phenotype. Our findings highlight the possible role of KMT2B as a gene involved in hereditary cerebellar ataxias.
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