Article

Brief Communication

Ann Lab Med 2022; 42(2): 274-277

Published online March 1, 2022 https://doi.org/10.3343/alm.2022.42.2.274

Copyright © Korean Society for Laboratory Medicine.

Detection Methods and Status of CAT Interruption of ATXN1 in Korean Patients With Spinocerebellar Ataxia Type 1

Ja-Hyun Jang, M.D. Ph.D.1 , Sun Joo Yoon, M.D.1 , Sun-Kyung Kim, M.T.1 , Jin Whan Cho, M.D.2,3 , and Jong-Won Kim, M.D.1

Departments of 1Laboratory Medicine and Genetics and 2Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Neuroscience Center, Samsung Medical Center, Seoul, Korea

Correspondence to: Ja-Hyun Jang, M.D., Ph.D.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: +82-2-3410-1890
Fax: +82-2-3410-0074
E-mail: jahyun.jang@gmail.com

Received: January 3, 2021; Revised: February 9, 2021; Accepted: September 17, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disease caused by abnormal CAG repeat expansion in the ataxin 1 gene (ATXN1). The presence of CAT interruption(s) is important for diagnosing SCA1 in patients with 39–44 repeat alleles, as only uninterrupted alleles are considered abnormal. Determining the CAT interruption status might also be important for patients with >44 repeats, as the length of the longest uninterrupted CAG repeat stretch has been correlated with age at SCA1 onset. We detected CAT interruption(s) in the archived samples of Korean SCA1 patients using a traditional restriction enzyme method and validated the usefulness of a fluorescence-based tethering PCR procedure. Among the 2,312 alleles analyzed from 1,156 patients, we found 17 expanded alleles with ≥39 repeats, 71% of which harbored 39–44 repeats. Restriction enzyme method of six samples (four with 39–44 repeats and two with >44 repeats) revealed that none of the expanded alleles had CAT interruption(s). Tethering PCR showed the characteristic electropherogram pattern expected without CAT interruption(s). Along with the enzyme restriction method, tethering PCR can be applied to determine the number of allele repeats and provide information on CAT interruption(s) in clinical laboratories.

Keywords: Spinocerebellar ataxia type 1, CAT interruption, Tethering PCR