Publications by authors named "Ejazullah Khan"

3 Publications

  • Page 1 of 1

Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family.

Mol Genet Genomic Med 2020 02 10;8(2):e1060. Epub 2020 Jan 10.

Diagnostic & Research Institute of Human Genetics, Medical University of Graz, Graz, Austria.

Background: Xeroderma pigmentosum (XP) is a rare genetic disorder, which is characterized by hyper-sensitivity to solar ultraviolet (UV) radiation. Clinical consequences of sun exposure are skin lesions and an increased risk of developing skin cancer. Genetic studies have identified eight genes associated with xeroderma pigmentosum. The proteins encoded by these genes are mainly involved in DNA repair mechanisms.

Methods: Molecular genetic characterization of patients with xeroderma pigmentosum involved positional cloning methods such as homozygosity mapping and subsequent candidate gene analysis. Mutation screening was performed through Sanger DNA sequencing.

Results And Discussion: In this case study, we report a novel protein truncating mutation in XPC associated with autosomal recessive xeroderma pigmentosum in a consanguineous Pakistani family. Genetic mapping revealed a novel single base insertion of a thymine nucleotide NM_004628.4: c.291dupT (c.291_292insT) in the second exon of XPC. The identified mutation leads to a premature stop codon (TGA) at amino acid position 98 (p.Asp98*) and thus presumably results in a truncated protein. The Xeroderma pigmentosum, complementation group C (XPC) is located on 3p25.1 and encodes a protein involved in nucleotide excision repair. The identified mutation presumably truncates all functional domains of the XPC protein, which likely results in the loss of protein function.

Conclusion: The study expands the knowledge of the mutational spectrum of XPC and is valuable for genetic counseling of affected individuals and their families.
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February 2020

Genetic studies of multiple consanguineous Pakistani families segregating oculocutaneous albinism identified novel and reported mutations.

Ann Hum Genet 2019 07 13;83(4):278-284. Epub 2019 Mar 13.

Gomal Centre of Biochemistry and Biotechnology, Gomal University, D.I. Khan, Pakistan.

Oculocutaneous albinism (OCA) is an autosomal-recessive disorder of a defective melanin pathway. The condition is characterized by hypopigmentation of hair, dermis, and ocular tissue. Genetic studies have reported seven nonsyndromic OCA genes, among which Pakistani OCA families mostly segregate TYR and OCA2 gene mutations. Here in the present study, we investigate the genetic factors of eight consanguineous OCA families from Pakistan. Genetic analysis was performed through single-nucleotide polymorphism (SNP) genotyping (for homozygosity mapping), whole exome sequencing (for mutation identification), Sanger sequencing (for validation and segregation analysis), and quantitative PCR (qPCR) (for copy number variant [CNV] validation). Genetic mapping in one family identified a novel homozygous deletion mutation of the entire TYRP1 gene, and a novel deletion of exon 19 in the OCA2 gene in two apparently unrelated families. In three further families, we identified homozygous mutations in TYR (NM_000372.4:c.1424G > A; p.Trp475*), NM_000372.4:c.895C > T; p.Arg299Cys), and SLC45A2 (NM_016180:c.1532C > T; p.Ala511Val). For the remaining two families, G and H, compound heterozygous TYR variants NM_000372.4:c.1037-7T > A, NM_000372.4:c.1255G > A (p.Gly419Arg), and NM_000372.4:c.1255G > A (p.Gly419Arg) and novel variant NM_000372.4:c.248T > G; (p.Val83Gly), respectively, were found. Our study further extends the evidence of TYR and OCA2 as genetic mutation hot spots in Pakistani families. Genetic screening of additional OCA cases may also contribute toward the development of Pakistani specific molecular diagnostic tests, genetic counseling, and personalized healthcare.
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July 2019

Ophthalmo-genetic analysis of Pakistani patients with nonsyndromic oculocutaneous albinism through whole exome sequencing.

J Pak Med Assoc 2017 May;67(5):790-792

Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, KPK, Pakistan.

Oculocutaneous albinism (OCA) is a disorder of defective melanin biosynthesis that is characterized by hypo-pigmentation of skin, hair and retinal pigment epithelium. Phenotypically, OCA patients exhibit white milky skin, whitish to golden hair and deterioration of retinal cells. Until recently, genetic studies have reported seven causative genes (TYR, TYRP1, OCA2, SLC45A2, SLC24A2, C10ORF11 and MCIR) and an uncharacterized OCA5 locus. Herein we present the medico-genetic study of three Pakistani patients inheriting autosomal recessive OCA. Whole exome sequencing, followed by Sanger DNA sequencing for segregation analysis, revealed recurrent mutations c.346C>T (p.Arg116*) and c.1255G>A (p.Gly419Arg) (family A and B respectively) in TYR gene, while the patient from family C did not reveal any known gene mutation, which suggests the involvement of some novel genetic factor. It is the first report of mapping c.346C>T mutation in a Pakistani patient. Our study further extends the evidence of genetic hotspots regions in TYR gene causing OCA in Pakistani population.
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May 2017