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
Methylenetetrahydrofolate reductase(MTHFR)deficiency is a rare autosomal recessive genetic disorder caused by mutations in the MTHFR gene,leading to a variety of clinical manifestations.In October 2022,the Second Xian...Methylenetetrahydrofolate reductase(MTHFR)deficiency is a rare autosomal recessive genetic disorder caused by mutations in the MTHFR gene,leading to a variety of clinical manifestations.In October 2022,the Second Xiangya Hospital of Central South University admitted a 21-year-old male patient with neuropsychiatric disorders,presenting primarily with cognitive decline,limb tremors,abnormal mental and behavioral symptoms,seizures,and gait disturbances.These symptoms had gradually developed over 5 years,worsening significantly in the past year.The patient’s plasma homocysteine levels were 10 times higher than normal,and brain MRI revealed brain atrophy and significant abnormal signals in the bilateral paraventricular nuclei and heads of the bilateral caudate nuclei.Further genetic testing identified a paternal mutation c.1604G>A(p.R535Q)and a maternal mutation c.227T>G(p.L76R)of the MTHFR gene.After betaine supplementation,the plasma homocysteine levels decreased within a week,and the symptoms improved.The patient was ultimately diagnosed with severe hyperhomocysteinemia due to MTHFR deficiency.The c.227T>G(p.L76R)mutation represents a novel missense mutation in the MTHFR gene associated with MTHFR deficiency,but further research is needed to confirm its potential pathogenicity.Early treatment with betaine can fully reverse the symptoms.展开更多
OBJECTIVES: To study the status of cochlear mitochondrial DNA (mtDNA) and to determine the location of mtDNA deletion in aged mice. METHODS: We detected cochlear mtDNA in 2, 7 - 10 and 17 - 19 month old mice by nested...OBJECTIVES: To study the status of cochlear mitochondrial DNA (mtDNA) and to determine the location of mtDNA deletion in aged mice. METHODS: We detected cochlear mtDNA in 2, 7 - 10 and 17 - 19 month old mice by nested polymerase chain reaction (PCR) and DNA sequencing. RESULTS: mtDNA3867bp deletions were found in the cochleae of aged mice. The deletion occurred within nt9103-nt12970 and were flanked by 15 base pair direct repeats. Comparing the incidence of mtDNA3867bp deletions, 17 - 19 month old mice (7/8) were significantly higher than 7 - 10 month old mice (4/16). The deletion was not observed in 2 month old mice (0/7). The ratio of deleted mtDNA/total mtDNA in 17 - 19 month old mice was higher than in 7 - 10 month old mice (P展开更多
Objective To detect new mutations among 29 glucose 6 phosphate dehydrogenase (G6PD) deficient individuals from Yunnan province Methods The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient ind...Objective To detect new mutations among 29 glucose 6 phosphate dehydrogenase (G6PD) deficient individuals from Yunnan province Methods The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient individuals Mutation was identified by single strand conformation polymorphism (SSCP), amplification created restriction site (ACRS), amplification refractory mutation system (ARMS) and DNA sequencing Results Among 29 cases, 18 cases of G1388A, 1 case of C1004A, and 1 case of G1381A were identified Nine cases remained to be defined The G1381A mutation is a novel mis sense mutation, with a substitution of threonine for alanine (A461T) The resultant G6PD had reduced enzymatic activity In addition, G1381A caused a restriction site of Stu I to disappear, providing a rapid method for the detection of this mutation Conclusion A novel mis sense mutation G1381A was found This mutation results in a substitution of threonine for alanine, producing enzyme with reduced activity The loss of the Stu I restriction site offers a rapid method for the detection of this mutation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supported by the National Natural Science Foundation(81971696)the Natural Science Foundation of Hunan Province(2022JJ30861),China.
文摘Methylenetetrahydrofolate reductase(MTHFR)deficiency is a rare autosomal recessive genetic disorder caused by mutations in the MTHFR gene,leading to a variety of clinical manifestations.In October 2022,the Second Xiangya Hospital of Central South University admitted a 21-year-old male patient with neuropsychiatric disorders,presenting primarily with cognitive decline,limb tremors,abnormal mental and behavioral symptoms,seizures,and gait disturbances.These symptoms had gradually developed over 5 years,worsening significantly in the past year.The patient’s plasma homocysteine levels were 10 times higher than normal,and brain MRI revealed brain atrophy and significant abnormal signals in the bilateral paraventricular nuclei and heads of the bilateral caudate nuclei.Further genetic testing identified a paternal mutation c.1604G>A(p.R535Q)and a maternal mutation c.227T>G(p.L76R)of the MTHFR gene.After betaine supplementation,the plasma homocysteine levels decreased within a week,and the symptoms improved.The patient was ultimately diagnosed with severe hyperhomocysteinemia due to MTHFR deficiency.The c.227T>G(p.L76R)mutation represents a novel missense mutation in the MTHFR gene associated with MTHFR deficiency,but further research is needed to confirm its potential pathogenicity.Early treatment with betaine can fully reverse the symptoms.
基金ThisworkwassupportedbygrantsfromtheNationalOutstandingYouthSciencesFoundationofChina (No 39725026)andthePostdoctoralSciencesFoundationofChina (No [2 0 0 0 ]23)
文摘OBJECTIVES: To study the status of cochlear mitochondrial DNA (mtDNA) and to determine the location of mtDNA deletion in aged mice. METHODS: We detected cochlear mtDNA in 2, 7 - 10 and 17 - 19 month old mice by nested polymerase chain reaction (PCR) and DNA sequencing. RESULTS: mtDNA3867bp deletions were found in the cochleae of aged mice. The deletion occurred within nt9103-nt12970 and were flanked by 15 base pair direct repeats. Comparing the incidence of mtDNA3867bp deletions, 17 - 19 month old mice (7/8) were significantly higher than 7 - 10 month old mice (4/16). The deletion was not observed in 2 month old mice (0/7). The ratio of deleted mtDNA/total mtDNA in 17 - 19 month old mice was higher than in 7 - 10 month old mice (P
基金ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 3 9670 40 1)
文摘Objective To detect new mutations among 29 glucose 6 phosphate dehydrogenase (G6PD) deficient individuals from Yunnan province Methods The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient individuals Mutation was identified by single strand conformation polymorphism (SSCP), amplification created restriction site (ACRS), amplification refractory mutation system (ARMS) and DNA sequencing Results Among 29 cases, 18 cases of G1388A, 1 case of C1004A, and 1 case of G1381A were identified Nine cases remained to be defined The G1381A mutation is a novel mis sense mutation, with a substitution of threonine for alanine (A461T) The resultant G6PD had reduced enzymatic activity In addition, G1381A caused a restriction site of Stu I to disappear, providing a rapid method for the detection of this mutation Conclusion A novel mis sense mutation G1381A was found This mutation results in a substitution of threonine for alanine, producing enzyme with reduced activity The loss of the Stu I restriction site offers a rapid method for the detection of this mutation
