Dataset Information

Rare and novel variants of PRKN and PINK1 genes in Vietnamese patients with early-onset Parkinson's disease.

ABSTRACT:

Background

Early-onset Parkinson's disease (EOPD) refers to that of patients who have been diagnosed or had onset of motor symptoms before age 50, accounting for 4% of Parkinson's disease patients. The PRKN and PINK1 genes, both involved in a metabolic pathway, are associated with EOPD.

Methods

To identify variants associated with EOPD, coding region of PARKIN and PINK1 genes in 112 patients and 112 healthy individuals were sequenced. Multiplex ligation-dependent probe amplification kit was used to determine EOPD patients that carried mutations in PRKN and PINK1 genes.

Results and conclusion

Three rare and three novel mutations in total of 14 variants of PARKIN and PINK1 were detected in the EOPD cohorts. Mutations of PRKN and PINK1 genes were found in five (4.4%) patients, which were four patients with compound heterozygous variants in the PRKN and one case with a homozygous mutation of the PINK1 gene. The novel mutations might reduce the stability of the PRKN and PINK1 protein molecules. The frequency of homozygous mutant genotype p.A340T of the PINK1 in the EOPD cohort was higher than in control (p = 0.0001, OR = 5.704), suggesting this variant might be a risk factor for EOPD. To the best of our knowledge, this is the first study of PRKN and PINK1 genes conducted on Vietnamese EOPD patients. These results might contribute to the genetic screening of EOPD in Vietnam.

SUBMITTER: Ton ND

PROVIDER: S-EPMC7549612 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Rare and novel variants of PRKN and PINK1 genes in Vietnamese patients with early-onset Parkinson's disease.

Ton Nguyen Dang ND Thuan Nguyen Duc ND Thuong Ma Thi Huyen MTH Ngoc Tran Thi Bich TTB Nhung Vu Phuong VP Hoa Nguyen Thi Thanh NTT Nam Nguyen Hoai NH Dung Hoang Thi HT Son Nhu Dinh ND Ba Nguyen Van NV Bac Nguyen Duy ND Tai Tran Ngoc TN Dung Le Thi Kim LTK Hung Nguyen Trong NT Duong Nguyen Thuy NT Ha Nguyen Hai NH Hai Nong Van NV

Molecular genetics & genomic medicine 20200827 10

<h4>Background</h4>Early-onset Parkinson's disease (EOPD) refers to that of patients who have been diagnosed or had onset of motor symptoms before age 50, accounting for 4% of Parkinson's disease patients. The PRKN and PINK1 genes, both involved in a metabolic pathway, are associated with EOPD.<h4>Methods</h4>To identify variants associated with EOPD, coding region of PARKIN and PINK1 genes in 112 patients and 112 healthy individuals were sequenced. Multiplex ligation-dependent probe amplificati ...[more]

PMID: 32856414

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Project description:Obesity is a multifactorial disorder with high heritability (50-75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in <1/2000 population controls) in 157 Spanish children with non-syndromic early-onset obesity (EOO: body mass index >3 standard deviations above the mean at <3 years of age) using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.

Dataset Information

Rare and novel variants of PRKN and PINK1 genes in Vietnamese patients with early-onset Parkinson's disease.

Background

Methods

Results and conclusion

Publications

Rare and novel variants of PRKN and PINK1 genes in Vietnamese patients with early-onset Parkinson's disease.

Similar Datasets

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