Mutations in DHDPSL are responsible for primary hyperoxaluria type III

Ruth Belostotsky, Eric Seboun, Gregory H. Idelson, Dawn S. Milliner, Rachel Becker-Cohen, Choni Rinat, Carla G. Monico, Sofia Feinstein, Efrat Ben-Shalom, Daniella Magen, Irith Weissman, Celine Charon, Yaacov Frishberg

Research output: Contribution to journalArticle

120 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)392-399
Number of pages8
JournalAmerican Journal of Human Genetics
Volume87
Issue number3
DOIs
StatePublished - Sep 10 2010

Fingerprint

Primary Hyperoxaluria
Mutation
4-hydroxy-2-oxoglutarate aldolase
glyoxylate reductase
Hyperoxaluria
Chromosomes, Human, Pair 10
Calcium Oxalate
Oxalates
Hydroxyproline
Missense Mutation
Microarray Analysis
Metabolic Networks and Pathways
Haplotypes
Genes
Single Nucleotide Polymorphism
Kidney

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Medicine(all)

Cite this

Belostotsky, R., Seboun, E., Idelson, G. H., Milliner, D. S., Becker-Cohen, R., Rinat, C., ... Frishberg, Y. (2010). Mutations in DHDPSL are responsible for primary hyperoxaluria type III. American Journal of Human Genetics, 87(3), 392-399. https://doi.org/10.1016/j.ajhg.2010.07.023

Mutations in DHDPSL are responsible for primary hyperoxaluria type III. / Belostotsky, Ruth; Seboun, Eric; Idelson, Gregory H.; Milliner, Dawn S.; Becker-Cohen, Rachel; Rinat, Choni; Monico, Carla G.; Feinstein, Sofia; Ben-Shalom, Efrat; Magen, Daniella; Weissman, Irith; Charon, Celine; Frishberg, Yaacov.

In: American Journal of Human Genetics, Vol. 87, No. 3, 10.09.2010, p. 392-399.

Research output: Contribution to journalArticle

Belostotsky, R, Seboun, E, Idelson, GH, Milliner, DS, Becker-Cohen, R, Rinat, C, Monico, CG, Feinstein, S, Ben-Shalom, E, Magen, D, Weissman, I, Charon, C & Frishberg, Y 2010, 'Mutations in DHDPSL are responsible for primary hyperoxaluria type III', American Journal of Human Genetics, vol. 87, no. 3, pp. 392-399. https://doi.org/10.1016/j.ajhg.2010.07.023
Belostotsky R, Seboun E, Idelson GH, Milliner DS, Becker-Cohen R, Rinat C et al. Mutations in DHDPSL are responsible for primary hyperoxaluria type III. American Journal of Human Genetics. 2010 Sep 10;87(3):392-399. https://doi.org/10.1016/j.ajhg.2010.07.023
Belostotsky, Ruth ; Seboun, Eric ; Idelson, Gregory H. ; Milliner, Dawn S. ; Becker-Cohen, Rachel ; Rinat, Choni ; Monico, Carla G. ; Feinstein, Sofia ; Ben-Shalom, Efrat ; Magen, Daniella ; Weissman, Irith ; Charon, Celine ; Frishberg, Yaacov. / Mutations in DHDPSL are responsible for primary hyperoxaluria type III. In: American Journal of Human Genetics. 2010 ; Vol. 87, No. 3. pp. 392-399.
@article{f7337215a0674f3791ca8912241dfb85,
title = "Mutations in DHDPSL are responsible for primary hyperoxaluria type III",
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.",
author = "Ruth Belostotsky and Eric Seboun and Idelson, {Gregory H.} and Milliner, {Dawn S.} and Rachel Becker-Cohen and Choni Rinat and Monico, {Carla G.} and Sofia Feinstein and Efrat Ben-Shalom and Daniella Magen and Irith Weissman and Celine Charon and Yaacov Frishberg",
year = "2010",
month = "9",
day = "10",
doi = "10.1016/j.ajhg.2010.07.023",
language = "English (US)",
volume = "87",
pages = "392--399",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Mutations in DHDPSL are responsible for primary hyperoxaluria type III

AU - Belostotsky, Ruth

AU - Seboun, Eric

AU - Idelson, Gregory H.

AU - Milliner, Dawn S.

AU - Becker-Cohen, Rachel

AU - Rinat, Choni

AU - Monico, Carla G.

AU - Feinstein, Sofia

AU - Ben-Shalom, Efrat

AU - Magen, Daniella

AU - Weissman, Irith

AU - Charon, Celine

AU - Frishberg, Yaacov

PY - 2010/9/10

Y1 - 2010/9/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77956393040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956393040&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2010.07.023

DO - 10.1016/j.ajhg.2010.07.023

M3 - Article

VL - 87

SP - 392

EP - 399

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -