在家族性和早发性帕金森病中扩展 PRKN 突变的范围。

Expanding the canvas of PRKN mutations in familial and early-onset Parkinson disease.

机构信息

Department of Neurology, Govind Ballabh Pant Postgraduate institute of medical education and research, New Delhi, 110002, India.

出版信息

Parkinsonism Relat Disord. 2019 Sep;66:216-219. doi: 10.1016/j.parkreldis.2019.08.005. Epub 2019 Aug 9.

DOI:10.1016/j.parkreldis.2019.08.005

PMID:31409571

Abstract

BACKGROUND

Mutations in PRKN (PARK2) are commonly encountered in early-onset Parkinson disease (PD).

OBJECTIVES

To screen for PRKN mutations in a clinically well-characterized cohort of early-onset PD patients with a family history (FEOPD; ≤50 years at onset) or sporadic (SEOPD; ≤50 years at onset) and late-onset familial patients (FLOPD; >50 years at onset).

METHODS

A total of 97 patients including 52 SEOPD and 45 familial PD (FEOPD: 23; FLOPD: 22) were screened for variants in PRKN by PCR- Sanger sequencing. PRKN dosage and variants in known PD genes were screened by qPCR and whole-exome sequencing in a subset of samples.

RESULTS

A total of 25 (25.77%) patients (SEOPD: 12, FEOPD: 6, and FLOPD: 7) were positive for PRKN variants. Of these, two patients manifested homozygous variants; while one patient was carrying three PRKN variants and two patients were carrying two PRKN variants. But, we could not examine their parents or relatives and their genotypes remain unknown. The remaining 20 (80%) patients were carrying heterozygous variants only. 32% of these variants were in exon 2, including a novel truncating homozygous variant (c.97C > T:p.Arg33Ter) in a SEOPD patient.

CONCLUSION

In our cohort, a novel homozygous variant (c.97C > T:p.Arg33Ter) in a patient with hyperhidrosis expands the spectrum of PRKN associated mutations. Furthermore, ~80% of the PRKN variants being heterozygous in this study cohort, implies the utility of the cohort for identification of additional novel/known causative PD gene(s).

摘要

背景

PRKN（PARK2）突变常见于早发性帕金森病（PD）。

目的

在具有家族史（FEOPD；发病年龄≤50 岁）或散发性（SEOPD；发病年龄≤50 岁）和晚发性家族性患者（FLOPD；发病年龄>50 岁）的早发性 PD 患者中，筛查 PRKN 突变。

方法

共对 97 例患者进行 PRKN 变异筛查，其中 52 例为 SEOPD，45 例为家族性 PD（FEOPD：23 例；FLOPD：22 例）。采用 PCR-Sanger 测序对 PRKN 进行变异筛查。在部分样本中，通过 qPCR 和全外显子组测序筛查 PRKN 剂量和已知 PD 基因的变异。

结果

共 25 例（25.77%）患者（SEOPD：12 例，FEOPD：6 例，FLOPD：7 例）存在 PRKN 变异。其中 2 例患者为纯合变异，1 例患者携带 3 个 PRKN 变异，2 例患者携带 2 个 PRKN 变异。但是，我们无法对他们的父母或亲属进行检查，他们的基因型仍然未知。其余 20 例（80%）患者仅携带杂合变异。其中 32%的变异位于外显子 2，包括 1 例 SEOPD 患者的新型纯合截断变异（c.97C>T:p.Arg33Ter）。