关键词: 亨廷顿病, 外显子组测序, 短串联重复, 儿童

Abstract:

Objective To report the clinic characteristic and genetic variant of a patient with childhood-onset Huntington disease (COHD), investigate the possibility of enhanced next-generation sequencing data to detect CAG repeat expansion and increase the outstanding of the disease through literature review. Method A COHD case was identified by exome sequencing combined with STR analysis (ES-STR), and the genetic and clinical date of the COHD patient were analyzed. Results The proband, a 16-year-old boy, presented with speech delay, hypokinesia and unsteady walking. ES analysis revealed 83 CAG repeats in Huntington gene (HTT) inherited from his father with 44 CAG repeats in HTT. In total, 15 articles and 20 patients related to COHD were included in literature review. Speech delay, dyskinesia, dystonia were major manifestations. The average onset was (4.23±2.33) years and the range of CAG repeat number of HTT gene was 51-312. ES demonstrated adequate coverage in the HTT locus and could identified cases with pathogenic expansion while large expansion needs additional validation to determine the precise repeat length. Conclusion The patient with COHD tended to have speech delay and movement disorder as the initial symptom instead of involuntary choreiform movements. ES-STR is an efficient diagnosis for Huntington disease (HD), particularly in COHD exhibiting non-classical phenotype. This article summarized the clinical features of COHD to improve the diagnosis for this rare disease and avoid undiagnosis and misdiagnosis.

Key words: Huntington disease, exome sequencing, short tandem repeat, child