Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase defici...Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase deficiency patients in China's Mainland diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis.A high proportion of atypical 3-oxo-4-bile acids in the urine indicated a deficiency in 4-3-oxosteroid 5β-reductase.All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents.One patient exhibited compound heterozygous mutations:c.396C>A and c.722A>T,while the other was heterozygous for the mutation c.797G>A.Based on these mutations,a diagnosis of primary 4-3-oxosteroid 5β-reductase deficiency could be confirmed.With ursodeoxycholic acid treatment and fat-soluble vitamin supplements,liver function tests normalized rapidly,and the degree of hepatomegaly was markedly reduced in both patients.展开更多
The genes for 5-1ipoxygenase activating protein （ALOX5AP） and phosphodiesterase 4D （PDE4D） have been demonstrated as susceptibility genes for lacunar in the Icelandic and Pakistani populations, but little is known...The genes for 5-1ipoxygenase activating protein （ALOX5AP） and phosphodiesterase 4D （PDE4D） have been demonstrated as susceptibility genes for lacunar in the Icelandic and Pakistani populations, but little is known about the role of these genes in Chinese populations. The present study utilized polymerase chain reaction and ligase detection reaction to detect single nucleotide polymorphisms （SNPs） in 280 consecutive stroke patients and 258 unrelated population-based controls from Nanjing, Jiangsu Province, China. The allele frequency, genotypes, and haplotypes of the two SNPs （rs456009 and rs966221） in PDE4D were similar between the two groups. However, A allele frequency of rs4073259 （A/G） and rs4769055 （A/C） in the ALOX5AP gene exhibited differences in two groups, and especially the haplotype of the SNP was significantly different between the two groups. Results suggested that the ALOX5AP gene might be involved in lacunar infarct, while PDE4D gene was not a risk factor for lacunar infarct in individuals from Jiangsu Province, China.展开更多
基金Supported by National Natural Science Foundation of China, No.81070281
文摘Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase deficiency patients in China's Mainland diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis.A high proportion of atypical 3-oxo-4-bile acids in the urine indicated a deficiency in 4-3-oxosteroid 5β-reductase.All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents.One patient exhibited compound heterozygous mutations:c.396C>A and c.722A>T,while the other was heterozygous for the mutation c.797G>A.Based on these mutations,a diagnosis of primary 4-3-oxosteroid 5β-reductase deficiency could be confirmed.With ursodeoxycholic acid treatment and fat-soluble vitamin supplements,liver function tests normalized rapidly,and the degree of hepatomegaly was markedly reduced in both patients.
基金the General Program of National Natural Science Foundation of China,No.30870125
文摘The genes for 5-1ipoxygenase activating protein （ALOX5AP） and phosphodiesterase 4D （PDE4D） have been demonstrated as susceptibility genes for lacunar in the Icelandic and Pakistani populations, but little is known about the role of these genes in Chinese populations. The present study utilized polymerase chain reaction and ligase detection reaction to detect single nucleotide polymorphisms （SNPs） in 280 consecutive stroke patients and 258 unrelated population-based controls from Nanjing, Jiangsu Province, China. The allele frequency, genotypes, and haplotypes of the two SNPs （rs456009 and rs966221） in PDE4D were similar between the two groups. However, A allele frequency of rs4073259 （A/G） and rs4769055 （A/C） in the ALOX5AP gene exhibited differences in two groups, and especially the haplotype of the SNP was significantly different between the two groups. Results suggested that the ALOX5AP gene might be involved in lacunar infarct, while PDE4D gene was not a risk factor for lacunar infarct in individuals from Jiangsu Province, China.
