Novel KMT2B mutation causes cerebellar ataxia: Expanding the clinical phenotype

被引:5
作者
Damasio, Joana [1 ,2 ,3 ]
Santos, Mariana [2 ]
Samoes, Raquel [1 ]
Araujo, Maria [4 ]
Macedo, Mafalda [4 ]
Sardoeira, Ana [1 ]
Cavaco, Sara [5 ]
Freitas, Joel [6 ]
Barros, Jose [1 ,7 ]
Oliveira, Jorge [2 ,3 ]
Sequeiros, Jorge [2 ,3 ,7 ]
机构
[1] Ctr Hosp Univ Porto, Neurol Dept, P-4099001 Porto, Portugal
[2] Univ Porto, I3S Inst Invest & Inovacao Saude, UnIGENe, Porto, Portugal
[3] Univ Porto, IBMC Inst Biol Mol & Celular, CGPP Ctr Genet Predit & Prevent, Porto, Portugal
[4] Ctr Hosp Univ Porto, Ophtalmol Dept, Porto, Portugal
[5] Ctr Hosp Univ Porto, Neuropsychol Unit, Porto, Portugal
[6] Ctr Hosp Univ Porto, Neurophysiol Dept, Porto, Portugal
[7] Univ Porto, ICBAS Sch Med & Biomed Sci, Porto, Portugal
关键词
cerebellar ataxia; dystonia; genetics; KMT2B;
D O I
10.1111/cge.14055
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:743 / 747
页数:5
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