In this study, we aimed to identify SYNE1-associated ataxia by whole exome sequencing in a Korean sample, and to review the prevalence of SYNE1 in non-French-Canadians.
Our findings support a genotype-phenotype correlation in SYNE1-ataxia and suggest the need for a systematic cardiologic evaluation in the setting of complicated spastic-ataxia phenotypes.
A definite molecular diagnosis was obtained in 5/10 families and included the following diseases: autosomal recessive spastic ataxia of Charlevoix-Saguenay, POLR3B-related hypomyelinating leukodystrophy, primary coenzyme Q10 deficiency type 4, Niemann-Pick disease type C1 and SYNE1-related ataxia.
Although this is a small sample of patients, these results suggest that SYNE1ataxia patients may represent a model to investigate effects of cerebellar degeneration in higher hierarchical cognitive functions.
SYNE1-ataxia is, therefore, a relatively common cause of recessive ataxia characterized by complex multisystemic neurostructural changes consistent with the phenotypic heterogeneity and neuroimaging configures a potential marker of the disease.
Various genes (eg, SPG7, SYNE1, PNPLA6) traditionally rooted in either the ataxia or hereditary spastic paraplegia classification system have now been shown to cause ataxia on the one end of the disease continuum and hereditary spastic paraplegia on the other.
There is a SYNE1 genotype-phenotype correlation emerging, with more proximal homozygous SYNE1 variants causing recessive cerebellar ataxia of variable onset (SCAR8; ARCA-1).
Nevertheless, recent studies on SYNE1ataxia have conveyed the condition from a geographically limited pure cerebellar recessive ataxia to a complex multisystem phenotype that is relatively common on the global scale.
Our findings, which present the largest systematic series of SYNE1 patients and mutations outside Canada, revise the view that SYNE1ataxia causes mainly a relatively pure cerebellar recessive ataxia and that it is largely limited to Quebec.
Our data indicate SYNE1 mutations are not an uncommon cause of recessive ataxia with or without additional clinical features in patients from various ethnicities.
Our findings, which present the largest systematic series of SYNE1 patients and mutations outside Canada, revise the view that SYNE1ataxia causes mainly a relatively pure cerebellar recessive ataxia and that it is largely limited to Quebec.
Here, we report a newly discovered form of recessive ataxia in a French-Canadian cohort and show that SYNE1 mutations are causative in all of our kindreds, making SYNE1 the first identified gene responsible for a recessively inherited pure cerebellar ataxia.
Here, we report a newly discovered form of recessive ataxia in a French-Canadian cohort and show that SYNE1 mutations are causative in all of our kindreds, making SYNE1 the first identified gene responsible for a recessively inherited pure cerebellar ataxia.