RESUMO
Primary hyperoxaluria type-III is a disorder of glyoxylate metabolism, caused by pathogenic variants in the HOGA1 gene. To date more than 50 disease-associated pathogenic sequence variants are identified in the gene. A few of the variants are population specific and are considered to have a founder effect in respective populations. The most prevalent variant, c.700+5G>T, identified frequently in Caucasian (allele frequency 0.63) and European (0.35) populations. Two variants, c.860G>T (p.Gly287Val) and c.944_946delAGG (p.Glu315del), account for 95% of the allele count in patients of Ashkenazi Jews ancestry. A possible mutational hot-spot at c.834 position is frequently found mutated in Chinese patients. This observed ethnic associations of HOGA1 alleles span a spectrum ranging from recurrence limited to an ethnic group to a possible founder-effect.
Assuntos
Hiperoxalúria Primária/genética , Oxo-Ácido-Liases/genética , Polimorfismo Genético , Etnicidade/genética , Efeito Fundador , Frequência do Gene , Humanos , Hiperoxalúria Primária/etnologiaRESUMO
A study was conducted on chronic renal failure patients treated by medications or by hemodialysis at The Martyr Dr. Khalil Sulaiman Hospital in Jenin city, Palestine, from 1/8/2005 to 1/8/2006 to know the underlying etiology of chronic renal failure. The subjects included were 84 patients. The information was obtained from files of the patients. The diagnosis was based on medical history, laboratory tests, X-rays, CT scans, ultrasound and renal biopsies. The results showed that the three most common causes of chronic renal failure in Jenin district were diabetes mellitus (33.32%), hypertension (16.7%), and chronic glomerulonephritis (13.1%). Inherited kidney diseases formed an important percentage (17.85%) and included primary hyperoxaluria (10.71%), Alport's syndrome (5.95%), and adult polycystic kidney disease (1.19%). These results differ from what is found in most developing countries including many Arab countries where the principal causes of chronic renal failure are chronic glomerulonephritis and interstitial nephritis. The high prevalence of inherited kidney diseases in some families (primary hyperoxaluria and Alport's) syndrome may be explained by the very high prevalence of consanguineous marriage especially among cousins in these families.
Assuntos
Árabes , Falência Renal Crônica/etiologia , Adulto , Árabes/genética , Consanguinidade , Nefropatias Diabéticas/etnologia , Nefropatias Diabéticas/etiologia , Predisposição Genética para Doença , Glomerulonefrite/complicações , Glomerulonefrite/etnologia , Humanos , Hiperoxalúria Primária/etnologia , Hiperoxalúria Primária/genética , Hipertensão/complicações , Hipertensão/etnologia , Falência Renal Crônica/etnologia , Falência Renal Crônica/genética , Oriente Médio/epidemiologia , Nefrite Hereditária/etnologia , Nefrite Hereditária/genética , Doenças Renais Policísticas/etnologia , Doenças Renais Policísticas/genética , Prevalência , Fatores de RiscoRESUMO
We report the clinical and genetic study of a primary hyperoxaluria type I (PH1) family with two sisters homozygous for p.Gly170Arg who are still asymptomatic at age 29 and 35, and two brothers, also homozygous for the same mutation, who are affected since age 27 and 30. The clear sex difference observed in this family and in others reported in the literature fits well with the prevalence of males over females in the Italian registry. In the KO model of PH1, only male mice develop renal stones, suggesting that the sex difference may affect both oxalate production and stone formation. A likely mechanism is the sex-related expression of glycolate oxidase shown in experimental animals. The stable isotope method recently developed by Huidekoper and van Woerden for in vivo assessment of the endogenous oxalate production could help to clarify the issue in humans.
Assuntos
Hiperoxalúria Primária/etnologia , Hiperoxalúria Primária/genética , Linhagem , Caracteres Sexuais , Adulto , Feminino , Homozigoto , Humanos , Itália , Masculino , MutaçãoRESUMO
Primary hyperoxaluria type 1 is an autosomal recessive inherited metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of phenotypes ranging from renal failure in infancy to mere renal stones in late adulthood. Mutations in the AGXT gene, encoding the liver-specific enzyme alanine:glyoxylate aminotransferase, are responsible for the disease. Seven mutations were detected in eight families in Israel. Four of these mutations are novel and three occur in children living in single-clan villages. The mutations are scattered along various exons (1, 4, 5, 7, 9, 10), and on different alleles comprising at least five different haplotypes. All but one of the mutations are in a homozygous pattern, reflecting the high rate of consanguinity in our patient population. Two affected brothers are homozygous for two different mutations expressed on the same allele. The patients comprise a distinct ethnic group (Israeli Arabs) residing in a confined geographic area. These results, which are supported by previous data, suggest for the first time that the phenomenon of multiple mutations in a relatively closed isolate is common and almost exclusive to the Israeli-Arab population. Potential mechanisms including selective advantage to heterozygotes, digenic inheritance, and the recent emergence of multiple mutations are discussed.
