AUTHOR=Zou Jinlong , Wang Fengyu , Gong Zhenping , Wang Runrun , Chen Shuai , Zhang Haohan , Sun Ruihua , Gao Chenhao , Li Wei , Shang Junkui , Zhang Jiewen 

TITLE=A Chinese SCA36 pedigree analysis of NOP56 expansion region based on long-read sequencing

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1110307

DOI=10.3389/fgene.2023.1110307

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> Spinocerebellar ataxias 36 (SCA36) is the neurodegenerative disease caused by the GGCCTG Hexanucleotide repeat expansions in <italic>NOP56</italic>, which is too long to sequence using short-read sequencing. Single molecule real time (SMRT) sequencing can sequence across disease-causing repeat expansion. We report the first long-read sequencing data across the expansion region in SCA36.</p><p><bold>Methods:</bold> We collected and described the clinical manifestations and imaging features of Han Chinese pedigree with three generations of SCA36. Also, we focused on structural variation analysis for intron 1 of the <italic>NOP56</italic> gene by SMRT sequencing in the assembled genome.</p><p><bold>Results:</bold> The main clinical features of this pedigree are late-onset ataxia symptoms, with a presymptomatic presence of affective and sleep disorders. In addition, the results of SMRT sequencing showed the specific repeat expansion region and demonstrated that the region was not composed of single GGCCTG hexanucleotides and there were random interruptions.</p><p><bold>Discussion:</bold> We extended the phenotypic spectrum of SCA36. We applied SMRT sequencing to reveal the correlation between genotype and phenotype of SCA36. Our findings indicated that long-read sequencing is well suited to characterize known repeat expansion.</p>