A NOVEL MISSENSE MUTATION (C.1982A>C) IN FCHSD1 GENE CAUSES AUTOSOMAL RECESSIVE EARLY ONSET PARKINSON’S DISEASE IN A CONSANGUINEOUS PAKISTANI FAMILY
Main Article Content
Keywords
Parkinson’s disease, FCHSD1, mTOR, Whole Exome Sequencing, Autosomal Recessive, Early Onset Parkinson disease
Abstract
Parkinson’s Disease (PD) is a neurodegenerative disorder characterized mainly by degenerative loss
of dopamine producing neurons and accumulation of alpha synuclein in substantia nigra pars
compacta (SNpc) of midbrain. Impairment of autophagy is believed to be common among multiple
neurodegenerative disorders. The disruption in autophagic process and improper removal of
accumulated proteins are linked with various neurodegenerative disorders including Parkinson’s
disease. Whole Exome Sequencing (WES) was done on extracted DNA of the patient having PD to
identify novel causative variants for underlying disorder. Identified variant was then validated in
other family members through Sanger’s sequencing. A novel missense variant
NM_033449.3:c.1982A>C (p.Asp661Ala) in FCHSD1 gene was identified through WES.
Segregation of the mutation in other family members was confirmed through Sanger’s sequencing.
The identified mutation (c.1982A>C) in FCHSD1 gene is responsible for autosomal recessive
Parkinson’s disease in a consanguineous Pakistani family.
Background: Parkinson’s Disease (PD) is a neurodegenerative disorder characterized mainly by
degenerative loss of dopamine producing neurons and accumulation of alpha synuclein in substantia
nigra pars compacta (SNpc) of midbrain. Impairment of autophagy is believed to be common
among multiple neurodegenerative disorders. The disruption in autophagic process and improper
removal of accumulated proteins are linked with various neurodegenerative disorders including
Parkinson’s disease.
Aims: The aim of this study was to describe the genetic variants responsible for Parkinson’s
Diseases in a consanguineous family.
Objective: To identify novel causative mutation responsible for autosomal recessive Parkinson’s
disease in a consanguineous Pakistani family.
Methods: Whole Exome Sequencing was done on extracted DNA to identify novel causative variants for underlying disorder. Identified variant was then validated in other family members
through Sanger’s sequencing.
Results: A novel missense variant NM_033449.3;c.1982A>C in FCHSD1 gene was identified
through Whole Exome Sequencing (WES). Segregation of the mutation was confirmed through
Sanger’s sequencing.
Conclusion: Identified mutation (c.1982A>C) in FCHSD1 gene is responsible for autosomal
recessive Parkinson’s disease in a consanguineous Pakistani family.
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Muhammad Umair
Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur
Muhammad Iqbal
Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur
Ghulam Mustafa
Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur
Munir Ahmad Bhinder
Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore
Muhammad Zuhaib Shah
Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur
Shahbaz Khan
Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur
Razia Parveen
Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur
Amir Ejaz
Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur
Hafiz Muhammad Azhar Baig
Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Department of
Ophthalmology, Harvard Medical School, Boston, MA, USA