Overexpanded CAG repeats in ATN1 cause an Early-Onset Case of Dentatorubral-Pallidoluysian atrophy with novel phenotypes and a literature Review of Chinese patients.

OBJECTIVE

Dentatorubral-pallidoluysian atrophy (DRPLA) is an inherited neurodegenerative disease caused by CAG overexpansion (≥48 tandem copies) in ATN1. The aim of this research was to explore the genetic cause of a large Chinese DRPLA pedigree and to review the characteristics of Chinese DRPLA patients.

METHODS

Suspected variants were screened by high-throughput sequencing. The number of CAG repeats was assessed by polymerase chain reaction using FAM-labeled primers followed by capillary electrophoresis. Literature on previously reported DRPLA cases with overexpanded ATN1 CAG repeats in China was reviewed.

RESULTS

After contracting a lung infection, the proband suffered early-onset DRPLA symptoms and novel phenotypes, transitioning from insomnia to stupor. The numbers of CAG repeats in the proband, her grandfather, father, mother, brother, and aunt were 8/81, 17/54, 10/57, 8/10, 10/10, and 10/17, respectively. Possible incomplete penetrance was observed in this pedigree.

CONCLUSION

We described a large Chinese DRPLA pedigree in which the proband carried the largest CAG expansion reported in China. We also reviewed the characteristics of Chinese DRPLA patients and broadened the phenotypic spectrum.