Mutations in DHDPSL are responsible for primary hyperoxaluria type III.
Am J Hum Genet
; 87(3): 392-9, 2010 Sep 10.
Article
en En
| MEDLINE
| ID: mdl-20797690
ABSTRACT
Primary hyperoxaluria (PH) is an autosomal-recessive disorder of endogenous oxalate synthesis characterized by accumulation of calcium oxalate primarily in the kidney. Deficiencies of alanine-glyoxylate aminotransferase (AGT) or glyoxylate reductase (GRHPR) are the two known causes of the disease (PH I and II, respectively). To determine the etiology of an as yet uncharacterized type of PH, we selected a cohort of 15 non-PH I/PH II patients from eight unrelated families with calcium oxalate nephrolithiasis for high-density SNP microarray analysis. We determined that mutations in an uncharacterized gene, DHDPSL, on chromosome 10 cause a third type of PH (PH III). To overcome the difficulties in data analysis attributed to a state of compound heterozygosity, we developed a strategy of "heterozygosity mapping"-a search for long heterozygous patterns unique to all patients in a given family and overlapping between families, followed by reconstruction of haplotypes. This approach enabled us to determine an allelic fragment shared by all patients of Ashkenazi Jewish descent and bearing a 3 bp deletion in DHDPSL. Overall, six mutations were detected four missense mutations, one in-frame deletion, and one splice-site mutation. Our assumption is that DHDPSL is the gene encoding 4-hydroxy-2-oxoglutarate aldolase, catalyzing the final step in the metabolic pathway of hydroxyproline.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hiperoxaluria Primaria
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Proteínas
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Oxo-Ácido-Liasas
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Mutación
Límite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Am J Hum Genet
Año:
2010
Tipo del documento:
Article
País de afiliación:
Israel