Founder effects of the homogentisate 1,2-dioxygenase (HGD) gene in a gypsy population and mutation spectrum in the gene among alkaptonuria patients from India

Danda, Sumita; Mohan, Sony; Devaraj, Prabavathi; Dutta, Atanu Kumar; Nampoothiri, Sheela; Yesodharan, Dhanya; Phadke, Shubha R.; Jalan, Anil; Thangaraj, Kumarasamy; Verma, I. C.; Danda, Debashish; Jebaraj, Isaac

doi:10.1007/s10067-020-05020-8

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…In the current study, the prevalence of pathogenic variants in the HGD gene was 100%. All affected members of the 4 candidate families were found to have the same pathogenic variant (c.365C>T) first reported by Phornphutkul et al (2002) and reported as the most common variant in Jordanian and Indian populations [14,16,18,20]. However, none of the other identified variants reported before (c.16-1G>, c.16-272_c.87+305del, c.87+8_88-31del765) in Jordanian population were found among the recruited families in the current study.…”

Section: Discussionsupporting

confidence: 76%

Variant Analysis of Alkaptonuria Families with Significant Founder Effect in Jordan

Khalil

Ali

Mwafi

et al. 2021

BioMed Research International

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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).

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Section: Discussionsupporting

confidence: 76%

Variant Analysis of Alkaptonuria Families with Significant Founder Effect in Jordan

Khalil

Ali

Mwafi

et al. 2021

BioMed Research International

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“…The biochemical diagnosis of alkaptonuria is based on the detection of substantial amounts of HGA (usually 1-8 g per day) in the urine 3 . Worldwide, the prevalence of Alkaptonuria is 1 in 250,000-100,000 live births 5 . The high prevalence rate has been reported in the regions of Slovakia and Dominican Republic, affecting 1 in 19,000 people 6 .…”

Section: Introductionmentioning

confidence: 99%

A Compendium of manually annotated genetic variants for Alkaptonuria-AKUHub

Akila¹,

T.C²,

Shofia³

et al. 2023

Preprint

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Alkaptonuria or 'black urine disease' is a rare autosomal recessive disorder caused by dysfunctional homogentisate 1,2-dioxygenase (HGD) gene (3q13.33) leading to accumulation of homogentisic acid in the body. This inborn error in metabolism of phenylalanine and tyrosine causes accumulation of homogentisic acid leading to ochronosis, pigmentation in the sclera, ear cartilage, mitral valve calcification and osteoarthropathy. Advances in sequencing technologies have helped us to map genetic variants associated with alkaptonuria in diverse populations and regions. Currently, no centralized resource of all the reported actionable variants with uniformity in annotation exists for the HGD gene. We have compiled HGD exonic variants from various data sources and systematically annotated their pathogenicity according to American College of Medical Genetics and the Association of Molecular Pathologists (ACMG/AMP) variant classification framework. A total of 1686 exonic variants were catalogued and manually curated, creating one of the most comprehensive Alkaptonuria variant databases (AKUHub) which is publicly available.

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