Genotype, phenotype and in silico pathogenicity analysis of HEXB mutations: Panel based sequencing for differential diagnosis of gangliosidosis

Mahdieh, N. and Mikaeeli, S. and Tavasoli, A.R. and Rezaei, Z. and Maleki, M. and Rabbani, B. (2018) Genotype, phenotype and in silico pathogenicity analysis of HEXB mutations: Panel based sequencing for differential diagnosis of gangliosidosis. Clinical Neurology and Neurosurgery, 167. pp. 43-53.

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Abstract

Objectives: Gangliosidosis is an inherited metabolic disorder causing neurodegeneration and motor regression. Preventive diagnosis is the first choice for the affected families due to lack of straightforward therapy. Genetic studies could confirm the diagnosis and help families for carrier screening and prenatal diagnosis. An update of HEXB gene variants concerning genotype, phenotype and in silico analysis are presented. Patients and Methods: Panel based next generation sequencing and direct sequencing of four cases were performed to confirm the clinical diagnosis and for reproductive planning. Bioinformatic analyses of the HEXB mutation database were also performed. Results: Direct sequencing of HEXA and HEXB genes showed recurrent homozygous variants at c.509G>A (p.Arg170Gln) and c.850C>T (p.Arg284Ter), respectively. A novel variant at c.416T>A (p.Leu139Gln) was identified in the GLB1 gene. Panel based next generation sequencing was performed for an undiagnosed patient which showed a novel mutation at c.1602C>A (p.Cys534Ter) of HEXB gene. Bioinformatic analysis of the HEXB mutation database showed 97 consistency of in silico genotype analysis with the phenotype. Bioinformatic analysis of the novel variants predicted to be disease causing. In silico structural and functional analysis of the novel variants showed structural effect of HEXB and functional effect of GLB1 variants which would provide fast analysis of novel variants. Conclusions: Panel based studies could be performed for overlapping symptomatic patients. Consequently, genetic testing would help affected families for patients� management, carrier detection, and family planning's. © 2018 Elsevier B.V.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: Article; bioinformatics; case report; clinical article; computer model; data base; differential diagnosis; female; gangliosidosis; gene; gene mutation; gene sequence; genetic variability; genotype; glb1 gene; hexa gene; hexb gene; homozygosity; human; infant; Iranian (citizen); male; Panel based sequencing; pathogenicity; phenotype; Sanger sequencing
Subjects: WH Hemic and Lymphatic Systems
Depositing User: eprints admin
Date Deposited: 18 Dec 2018 09:59
Last Modified: 17 Aug 2019 05:32
URI: http://eprints.iums.ac.ir/id/eprint/6740

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