Clinical and genetic study of one DRPLA case

Abstract

Objective To investigate the clinical and genetic features of dentatorubral ⁃ pallidoluysian atrophy (DRPLA). Methods The trinucleotide repeats of spinocerebellar ataxia (SCA) disease genes were detected by polymerase chain reaction (PCR) initially in 388 SCA cases which included 234 cases with autosomal dominant inheritance and 154 sporadic cases. Fragment analysis with laser ⁃ induced fluorescence in capillary electrophoresis was performed for the samples with 2 bands detected by agarose gel electrophoresis (AGE). The repeat numbers of the positive or suspicious samples were verified by the pUC18⁃T vector cloning and sequencing. Results Based on the 2 methods, the cytosine⁃adenine⁃ guanine (CAG) repeat expansion of DRPLA gene was detected in one female case with mild ataxia and suspected seizure. The repeat numbers of the 2 alleles were 14 and 54 by fragment analysis, and 15 and 58 by cloning sequencing. The 2 members of her family had a history of seizure, but no obvious ataxia. The CAG repeat numbers of the other 19 cases without abnormal expansions ranged from 7 to 20, of which 9 was common. Conclusion The patient's atypical manifestations suggests that clinical variation may exist in DRPLA. Only one case of DRPLA is found in 388 SCA cases, indicating that DRPLA may be a relatively rare subtype of SCA in Chinese population. The secondary structure of DNA owing to the highly repetitive sequences will induce DNA polymerase sliding during the amplification, which will reduce the fidelity in DNA replication. This problem exists in both fragment analysis and cloning sequencing. For the latter method, the instability also appears in the process of cloning. Therefore, the repeat numbers need to be mutually verified by the 2 methods.

DOI：10.3969/j.issn.1672-6731.2010.06.012