Variant Analysis of Alkaptonuria Families with Significant Founder Effect in Jordan
Autor: | Raida Khalil, Eman Albsoul, Nesrin Mwafi, Arwa Alsaraireh, Ibrahim Al Sbou, Dema Ali, Loiy Obeidat |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Oligonucleotides 030105 genetics & heredity Alkaptonuria chemistry.chemical_compound Exon Medicine Missense mutation Child Homogentisic Acid Sanger sequencing Genetics Metabolic disorder Exons General Medicine Middle Aged Founder Effect Pedigree Child Preschool symbols Female Research Article Adult Heterozygote Adolescent Article Subject Mutation Missense Genes Recessive General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences symbols.namesake Humans Homogentisic acid Family Health Homogentisate 1 2-Dioxygenase Ochronosis Jordan General Immunology and Microbiology business.industry Genetic Variation Sequence Analysis DNA medicine.disease 030104 developmental biology chemistry business Founder effect |
Zdroj: | BioMed Research International BioMed Research International, Vol 2021 (2021) |
ISSN: | 2314-6133 |
DOI: | 10.1155/2021/1515641 |
Popis: | Background. Metabolic disorder alkaptonuria is an autosomal recessive disorder caused by mutations in the HGD gene, and a deficiency HGD enzyme activity results in an accumulation of homogentisic acid (HGA), ochronosis, and destruction of connective tissue. Methods. We clinically evaluated 18 alkaptonuria patients (age range, 3 to 60 years) from four unrelated families. Furthermore, 11 out of 18 alkaptonuria patients and 7 unaffected members were enrolled for molecular investigations by utilizing Sanger sequencing to identify variants of the 14 exons of HGD gene. Results. We found that the seven patients from the 4 unrelated families carried a recurrent pathogenic missense variant (c.365C>T, p. Ala122Val) in exon 6 of HGD gene. The variant was fully segregated with the disease in affected family members while the other unaffected family members were heterozygous carriers for this variant. Additionally, the clinical features were fully predicted with alkaptonuria disorder. Conclusion. In this study, we confirmed that the most common variants in Jordanian AKU patients was c.365C>T, p. Ala122Val in exon 6 of HGD gene. Additionally, we correlated the clinical and genetic features of AKU patients at various ages (3-60 years). |
Databáze: | OpenAIRE |
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