PMID- 10541294
OWN - NLM
STAT- MEDLINE
DCOM- 19991118
LR  - 20210518
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 10
IP  - 11
DP  - 1999 Nov
TI  - Primary hyperoxaluria type I: a model for multiple mutations in a monogenic
      disease within a distinct ethnic group.
PG  - 2352-8
AB  - 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.
FAU - Rinat, C
AU  - Rinat C
AD  - Division of Pediatric Nephrology, Shaare Zedek Medical Center and Hebrew
      University, Hadassah School of Medicine, Jerusalem, Israel.
FAU - Wanders, R J
AU  - Wanders RJ
FAU - Drukker, A
AU  - Drukker A
FAU - Halle, D
AU  - Halle D
FAU - Frishberg, Y
AU  - Frishberg Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
SB  - IM
MH  - Arabs
MH  - Child, Preschool
MH  - Haplotypes
MH  - Humans
MH  - Hyperoxaluria, Primary/ethnology/*genetics
MH  - Infant
MH  - Israel
MH  - *Point Mutation
MH  - Polymorphism, Genetic
EDAT- 1999/11/30 00:00
MHDA- 1999/11/30 00:01
CRDT- 1999/11/30 00:00
PHST- 1999/11/30 00:00 [pubmed]
PHST- 1999/11/30 00:01 [medline]
PHST- 1999/11/30 00:00 [entrez]
AID - 10.1681/ASN.V10112352 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 1999 Nov;10(11):2352-8. doi: 10.1681/ASN.V10112352.