Tags

Type your tag names separated by a space and hit enter

Clinical features and genetic characteristics of homozygous spinocerebellar ataxia type 3.
Mol Genet Genomic Med. 2020 Jul 09 [Online ahead of print]MG

Abstract

BACKGROUND

Homozygous spinocerebellar ataxia type 3 (SCA3) patients, which have an expanded cytosine-adenine-guanine (CAG) repeat mutation in both alleles of ATXN3, are extremely rare. Clinical features and genetic characteristics of them were seldom studied.

METHODS

We analyzed seven newly homozygous SCA3 patients from five families and 14 homozygotes reported previously. An additional cohort of 30 heterozygous SCA3 patients were analyzed to compare age at onset (AAO).

RESULTS

Two out of seven SCA3 homozygotes had the minimum CAG repeats reported so far (55/56 and 56/58). Five patients appeared peripheral neuropathy and two had mild cognitive impairment. The AAO was significantly inversely correlated with both the large and small expanded CAG repeats (r = -.7682, p < .0001). The AAO was significantly earlier in homozygous SCA3 than heterozygous ones (32.81 ± 11.86 versus. 49.90 ± 9.73, p < .0001). In addition, the AAO of our seven homozygotes is elder compared to those reported previously (41.29 years vs. 28.57 years), which may be related to the fewer CAG repeats in our seven patients.

CONCLUSION

Gene dosage effect may play an important role in the AAO and severity of disease, and homozygosity for ATXN3 enhances phenotypic severity. Our findings expand clinical features and genetic characteristics of homozygous SCA3 patients.

Authors+Show Affiliations

Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.Department of Neurology and Institute of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32643267

Citation

Li, Quan-Fu, et al. "Clinical Features and Genetic Characteristics of Homozygous Spinocerebellar Ataxia Type 3." Molecular Genetics & Genomic Medicine, 2020, pp. e1314.
Li QF, Cheng HL, Yang L, et al. Clinical features and genetic characteristics of homozygous spinocerebellar ataxia type 3. Mol Genet Genomic Med. 2020.
Li, Q. F., Cheng, H. L., Yang, L., Ma, Y., Zhao, J. J., Dong, Y., & Wu, Z. Y. (2020). Clinical features and genetic characteristics of homozygous spinocerebellar ataxia type 3. Molecular Genetics & Genomic Medicine, e1314. https://doi.org/10.1002/mgg3.1314
Li QF, et al. Clinical Features and Genetic Characteristics of Homozygous Spinocerebellar Ataxia Type 3. Mol Genet Genomic Med. 2020 Jul 9;e1314. PubMed PMID: 32643267.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical features and genetic characteristics of homozygous spinocerebellar ataxia type 3. AU - Li,Quan-Fu, AU - Cheng,Hao-Ling, AU - Yang,Lu, AU - Ma,Yin, AU - Zhao,Jing-Jing, AU - Dong,Yi, AU - Wu,Zhi-Ying, Y1 - 2020/07/09/ PY - 2020/02/08/received PY - 2020/04/26/revised PY - 2020/04/28/accepted PY - 2020/7/10/entrez KW - clinical features KW - gene dosage KW - homozygous KW - spinocerebellar ataxia type 3 SP - e1314 EP - e1314 JF - Molecular genetics & genomic medicine JO - Mol Genet Genomic Med N2 - BACKGROUND: Homozygous spinocerebellar ataxia type 3 (SCA3) patients, which have an expanded cytosine-adenine-guanine (CAG) repeat mutation in both alleles of ATXN3, are extremely rare. Clinical features and genetic characteristics of them were seldom studied. METHODS: We analyzed seven newly homozygous SCA3 patients from five families and 14 homozygotes reported previously. An additional cohort of 30 heterozygous SCA3 patients were analyzed to compare age at onset (AAO). RESULTS: Two out of seven SCA3 homozygotes had the minimum CAG repeats reported so far (55/56 and 56/58). Five patients appeared peripheral neuropathy and two had mild cognitive impairment. The AAO was significantly inversely correlated with both the large and small expanded CAG repeats (r = -.7682, p < .0001). The AAO was significantly earlier in homozygous SCA3 than heterozygous ones (32.81 ± 11.86 versus. 49.90 ± 9.73, p < .0001). In addition, the AAO of our seven homozygotes is elder compared to those reported previously (41.29 years vs. 28.57 years), which may be related to the fewer CAG repeats in our seven patients. CONCLUSION: Gene dosage effect may play an important role in the AAO and severity of disease, and homozygosity for ATXN3 enhances phenotypic severity. Our findings expand clinical features and genetic characteristics of homozygous SCA3 patients. SN - 2324-9269 UR - https://www.unboundmedicine.com/medline/citation/32643267/Clinical_features_and_genetic_characteristics_of_homozygous_spinocerebellar_ataxia_type_3 L2 - https://doi.org/10.1002/mgg3.1314 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.