Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome 8q by homozygosity mapping

Hamida, Christiane Ben; Doerflinger, Nathalie; Belal, Samir; Linder, C.Y.; Reutenauer, Laurence; Dib, Colette; Gyapay, Gábor; Vignal, Alain; Paslier, Denis Le; Cohen, Daniel

doi:10.1038/ng1093-195

Cited by 194 publications

(87 citation statements)

References 28 publications

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“…This suggests heterogeneity within this group (or even digenic inheritance), with ALDR being a good candidate for interaction with PMP70. A possible implication of ALDR in Zellweger syndrome may be easily tested by homozygosity mapping in consanguineous families (37)(38)(39), using microsatellites located close to the human ALDR gene, or by complementation analysis in patients cells using an ALDR expression vector.…”

Section: Discussionmentioning

confidence: 99%

A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern.

Lombard-Platet¹,

Savary²,

Sarde³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

204

132

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Adrenoleukodystrophy (ALD), a severe demyelinating disease, is caused by mutations in a gene coding for a peroxisomal membrane protein (ALDP), which belongs to the superfamily of ATP binding cassette (ABC) transporters and has the structure of a half transporter. ALDP showed 38% sequence identity with another peroxisomal membrane protein, PMP70, up to now its closest homologue. We describe here the cloning and characterization of a mouse ALD-related gene (ALDR), which codes for a protein with 66% identity with ALDP and shares the same half transporter structure. The ALDR protein was overexpressed in COS cells and was found to be associated with the peroxisomes. The ALD and ALDR genes show overlapping but clearly distinct expression patterns in mouse and may thus play similar but nonequivalent roles. The ALDR gene, which appears highly conserved in

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Section: Discussionmentioning

confidence: 99%

A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern.

Lombard-Platet¹,

Savary²,

Sarde³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

204

132

View full text Add to dashboard Cite

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“…This information was included in two-point lod score calculation by considering the non-recombinant haplotype as a single Mapping of two recessive ataxia loci P Bomont et al y locus. 14 The frequency of the homozygous haplotype was calculated as the product of the frequency of the individual alleles estimated from the reference population in the relevant countries. In order to eliminate bias due to possible linkage disequilibrium, only one marker was taken into account when two were located at the same position on the genetic map.…”

Section: Linkage Analysismentioning

confidence: 99%

Homozygosity mapping of spinocerebellar ataxia with cerebellar atrophy and peripheral neuropathy to 9q33–34, and with hearing impairment and optic atrophy to 6p21–23

et al. 2000

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With the availability of a simple molecular test that distinguishes Friedreich ataxia, the most frequent form of inherited ataxia, from other recessive ataxias, it now becomes possible to unravel the genetic heterogeneity of the latter. We have now localised two genes causing autosomal recessive spinocerebellar ataxia in two consanguineous families. In the first family, the four affected Japanese sibs had spinocerebellar ataxia associated with elevated levels of serum creatine kinase, γ-globulin, and α-foetoprotein. Homozygosity over a 20 cM region allowed to demonstrate linkage at 9q33.3-34.3 with a lod score of 3.0. Genotyping two unrelated Japanese patients from first degree consanguineous parents revealed that one was homozygous for the same region but did not share the biochemical features. In the second family, an Israeli uncle and a niece were affected by an early-onset recessive ataxia and subsequently developed hearing impairment and optic atrophy. Homozygosity over a 17 cM region allowed demonstration of linkage at 6p21-23 with a lod score of 3.25. These two localisations of autosomal recessive ataxia genes represent a first step toward the identification of genetically homogenous, non-Friedreich, ataxic patients and subsequent cloning of the genes. European Journal of Human Genetics (2000) 8, 986-990.

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“…It has now been established that ␣ -TTP, through this mechanism, is a major determinant of plasma ␣ -tocopherol level. In fact, humans with a defective ␣ -TTP gene have severe vitamin E deficiency ( 2 ), and depletion of the ␣ -TTP gene in mice results in severely reduced plasma and tissue ␣ -tocopherol concentrations (3)(4)(5). Although genetic ␣ -TTP deficiency severely affects serum and peripheral tissue ␣ -tocopherol concentrations, effects of the reduction of hepatic ␣ -TTP level on serum or liver ␣ -tocopherol under physiological conditions have been reported in only a very few cases ( 6 , 7 ).…”

mentioning

confidence: 99%

Galactosamine-Induced Acute Liver Injury in Rats Reduces Hepatic .ALPHA.-Tocopherol Transfer Protein Production

Takenaka

Kita

Ikeya

et al. 2007

J Nutr Sci Vitaminol

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SummaryThe liver plays the main role in the secretion of food-derived ␣ -tocopherol into the circulation through the functioning of ␣ -tocopherol transfer protein ( ␣ -TTP). However, the effect of liver disease on ␣ -TTP level and ␣ -tocopherol metabolism has not been clarified. We examined the amount of liver ␣ -TTP and its effect on serum ␣ -tocopherol concentration in liver injury. Male Wistar rats were injected intraperitoneally with D -galactosamine at 800 mg/kg body weight, and liver and serum lipid concentrations, ␣ -tocopherol concentrations, and hepatic ␣ -TTP mRNA and protein levels were measured at 24, 48, and 72 h after injection. On the basis of body weight changes and serum transaminase activities, the livers were found to be in an injured state 24 and 48 h after galactosamine injection but had recovered by 72 h. The hepatic ␣ -TTP mRNA level was reduced throughout the experimental period, and at 48 h after injection the ␣ -TTP protein level had begun to decrease. Lipid and ␣ -tocopherol concentrations in the serum were decreased at 24 and 48 h after injection and increased at 72 h. Liver lipid concentrations were increased at 24 and 48 h after injection, but the liver ␣ -tocopherol concentration was unchanged. These results show that galactosamine-induced liver injury decreases hepatic ␣ -TTP synthesis in rats. Serum ␣ -tocopherol concentration was not directly affected by the acute change in hepatic ␣ -TTP level, suggesting that the chronic changes in ␣ -TTP activity would be necessary to regulate serum ␣ -tocopherol concentration.

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Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome 8q by homozygosity mapping

Cited by 194 publications

References 28 publications

A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern.

A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern.

Homozygosity mapping of spinocerebellar ataxia with cerebellar atrophy and peripheral neuropathy to 9q33–34, and with hearing impairment and optic atrophy to 6p21–23

Galactosamine-Induced Acute Liver Injury in Rats Reduces Hepatic .ALPHA.-Tocopherol Transfer Protein Production

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