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Identification of a novel mutation in ADRBK1 in a kindred with an autosomal dominant cerebellar ataxia
thesisposted on 2022-03-28, 16:48 authored by Ronald C. H. Siu
A novel mutation in the gene ARDBK1 (OMIM 109365) was identified in a kindred with autosomal dominant cerebellar ataxia (ADCA). An Australian family was found to have a unique phenotype of ADCA characterized by a slowly progressive cerebellar ataxia and dysarthria without oculomotor abnormalities. Ten family members (five symptomatic, four asymptomatic and one obligate carrier) participated. All subjects underwent clinical examination, MRI scanning of the brain and exome sequencing. Cerebellar atrophy without brainstem involvement was identified on MRI in both symptomatic and some asymptomatic subjects. DNA was extracted, sequenced and aligned with reference genetic information. A mutation in ADRBK1 was identified in nine subjects: all of the symptomatic and some of the asymptomatic subjects. The mutation in ADRBK1 is predicted to produce an amino acid change from Isoleucine (ATT) to Methionine (ATG) at position 140. This novel mutation in ADRBK1 requires further study to prove biological relevance in ADCA.