ABSTRACT
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).
Subject(s)
Alkaptonuria/genetics , Family Health , Founder Effect , Genes, Recessive , Homogentisate 1,2-Dioxygenase/genetics , Ochronosis/genetics , Adolescent , Adult , Child , Child, Preschool , Exons , Female , Genetic Variation , Heterozygote , Homogentisic Acid/metabolism , Humans , Jordan , Male , Middle Aged , Mutation, Missense , Oligonucleotides , Pedigree , Sequence Analysis, DNA , Young AdultABSTRACT
BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic disease characterized by widespread body pain, weakness in certain parts of the body (critical points), low pain tolerance, sleep disturbances, and fatigue. This syndrome is considered rare in Jordan. OBJECTIVES: The research aimed to find out the association of the angiotensin converting enzyme, methylenetetrahydrofolate reductase, and vitamin D receptor (ACE, MHFTR, and VDR, respectively) genotypes with FMS among Jordanian patients. METHODS: This work included 22 FM patients and 22 healthy individuals of Jordanian Arabic origin. The ACE rs4646994, MTHFR rs1801133, and VDR rs2228570 genotypes were determined using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism. RESULTS: No associations between ACE rs4646994, MTHFR rs1801133, and VDR rs2228570 with the vulnerability of a person for the development of FMS were found. However, we found an association between the ACE rs4646994 genotype and restless leg among FM patients. CONCLUSION: Based on the result from this study, it appears that the ACE rs4646994 genotype is associated with restless leg among FMS patients of Jordanian origin. Further clinical investigations with larger sample sizes are required to confirm these findings and understand the molecular mechanism of ACE rs4646994 genetic variant in the restless leg syndrome among FM patients.
