Abstract
Two affected and one unaffected siblings from a French-Canadian family were evaluated in our neurogenetic clinic. The oldest brother had intentional and postural hand tremor while his youngest sister presented mild ataxia, a similar hand tremor and global developmental delay. Brain MRIs of the two affected family members further revealed a significant cerebellar atrophy. For this study we conducted a whole exome sequencing (WES) investigation using genomic DNA prepared from the affected brother and sister, alongside DNA prepared from their unaffected mother, and identified two mutations previously reported to cause a rare disorder known as Congenital Disorder of Glycosylation, type Ia (CDG1A) (OMIM #212065). This study emphasizes how the diagnosis of patients presenting a mild tremor phenotype associated with cerebellar atrophy may benefit from WES in establishing genetic defects associated with their conditions.
Highlights
The hereditary cerebellar ataxias are a clinically and genetically heterogeneous group of disorders, where the cerebellum is predominantly affected
The classification of spinocerebellar ataxias has been a subject of debate for several years and in 1988 Harding proposed a first ordering [1]
Since the advent of high-throughput sequencing technologies, prodigious advances have been made in human genetics and the classification and management of hereditary cerebellar ataxias has been transformed [2]
Summary
The hereditary cerebellar ataxias are a clinically and genetically heterogeneous group of disorders, where the cerebellum is predominantly affected. Case presentation Index family: Our family was selected according the FORGE criteria mainly for the presence of a clear recessive mode of inheritance, an early age of onset and at least two affected family members with Canadian origins This family (Figure 1) was seen at two different time point: for the first time in 2004 and later in 2012, where they underwent clinical evaluation by a neurologist (ND). In 2004, the first case (Figure 1, Individual II-1) was 20 years of age, and was seen for one principal feature: upper limb tremor This boy was born after a normal pregnancy, normal delivery and with normal APGARS. Magnetic brain imaging (MRI) revealed cerebellar atrophy (Figure 2), localised at the cerebellar hemispheres and the vermis Her sister (Figure 1, Individual II-2) was 10 years of age at the first neurological examination. The two mutations were confirmed by Sanger sequencing, in all individuals available in this family
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