title: Mutational spectrum of Xeroderma pigmentosum group A in Egyptian patients.
abstract: Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease characterized by hyperphotosensitivity, DNA repair defects and a predisposition to skin cancers. The most frequently occurring type worldwide is the XP group A (XPA). There is a close relationship between the clinical features that ranged from severe to mild form and the mutational site in XPA gene. The aim of this study is to carry out the mutational analysis in Egyptian patients with XP-A. This study was carried out on four unrelated Egyptian XP-A families. Clinical features were examined and direct sequencing of the coding region of XPA gene was performed in patients and their parents. Direct sequencing of the whole coding region of the XPA gene revealed the identification of two homozygous nonsense mutations: (c.553C >T; p.(Gln185)) and (c.331G>T; p.(Glu111)), which create premature, stop codon and a homodeletion (c.374delC: p.Thr125Ilefs 15) that leads to frameshift and premature translation termination. We report the identification of one novel XPA gene mutation and two known mutations in four unrelated Egyptian families with Xermoderma pigmentosum. All explored patients presented severe neurological abnormalities and have mutations located in the DNA binding domain. This report gives insight on the mutation spectrum of XP-A in Egypt. This would provide a valuable tool for early diagnosis of this severe disease.
authors.affiliation: Medical Molecular Genetics Department, Human Genetics & Genome Research Division, National Research Center, Cairo, Egypt.
authors.forename: Khalda
authors.initials: K
authors.lastname: Amr
authors.forename: Olfa
authors.initials: O
authors.lastname: Messaoud
authors.forename: Mohamad
authors.initials: M
authors.lastname: El Darouti
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.forename: Ghada
authors.initials: G
authors.lastname: El-Kamah
mesh_terms: D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004534:Egypt; D005260:Female; D006801:Humans; D008297:Male; D014983:Xeroderma Pigmentosum / Q000235:genetics*; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D051760:Xeroderma Pigmentosum Group A Protein
keywords: +ve; A; Adenine; Amino acid; C; Clinical correlation to mutation location; Cytosine; DNA; Deletion; Deoxyribonucleic acid; F; Female; Fig; Figure; G; Guanine; KD; Kilo Dalton; M; MR; Male; Mental retardation; NER; Novel mutation; Nucleotide excision repair; OMIM; Online Mendelian Inheritance in Man; PCR; Polymerase chain reaction; Positive; RNA; Ribonucleic acid; T; Thymine; XP; XP-A; XP-C; XP-G; Xeroderma pigmentosum; Xeroderma pigmentosum group A; Xeroderma pigmentosum group C; Xeroderma pigmentosum group G; Xeroderma pigmentosum-group A; aa; del