Mutation analysis of SLC12A1 gene in nine Chinese patients with Bartter syndrome type Ⅰ / 中华肾脏病杂志

Objective To analyze the mutations of SLC12A1 gene in nine Chinese families with Bartter syndrome type I (BS1),and analyze the relationship between genotype and phenotype.Methods The next generation sequencing was used to detect mutations in nine BS1 patients including eight with antenatal BS (aBS) and one with classical BS (cBS).Clinical characteristics and biochemical findings at the first admission as well as follow-up were reviewed.Results 15 different mutations of SLC12A1 gene were identified,including 11 novel ones.Among nine probands,seven were compound heterozygotes,two were homozygotes.All patients presented with polydipsia and polyuria,and eight with growth retardation.All patients had lower than-normal serum chloride concentration,metabolic alkalosis,and elevated basal renin activity and aldosterone,and seven had hypokalemia.Through treatment of indomethacin and/or potassium chloride,biochemical indicators could roughly restored normal.Conclusion These findings will enrich the human gene mutation database (HGMD) and provide valuable references to the genetic counseling and diagnosis for Chinese population.

Mutation analysis of 5 children with primary distal renal tubular acidosis / 中华肾脏病杂志

Objective To analyze the mutations of causal genes in 5 children with primary distal renal tubular acidosis (dRTA),and explore their association of genotype and phenotype,so as to raise the awareness of the disease.Methods The whole exome sequencing was used to identify mutations in these 5 children from 5 families.Results A total of 4 different mutations of ATP6V0A4 gene were found in 2 dRTA children,including a novel heterozygous intron mutation (c.639 + 1G＞ A),a reported heterozygous nonsense variant (c.580C ＞T,p.Arg194*) and 2 novel heterozygous duplications (c.1504dupT,p.Tyr502Leufs*22;c.2351dupT,p.Phe785Ilefs*28).Two novel heterozygous missense mutations of ATP6V 1B 1 gene (c.409C ＞ T,p.Pro 137Ser;c.904C ＞ T,p.Arg302Trp) were identified in the third child,and a heterozygous missense mutation of SLC4A1 gene (c.1765C ＞ A,p.Arg589Ser) previously reported was found in the fourth child.No mutation of the dRTA-related causal genes was found in the fifth child.Furthermore,the mutations of causal genes in each of the first three children were compound heterozygous,which were consistent with the autosomal recessive inheritance pattern,and the variant from the fourth child was de novo.Conclusions The present study has found 7 mutations,including 5 novel variants,which enriches the human gene mutation database (HGMD) and contributes to a better understanding of the disease mechanisms.

Genotype, phenotype, and follow-up of Chinese patients with Gitelman's syndrome / 中华内分泌代谢杂志

Objective To analyze the characteristics of the genotype, phenotype, and follow-up of Gitelman's syndrome (GS) in the largest group of Chinese patients. Methods Sixty seven patients with GS underwent SLC12A3 gene analysis. Clinical characteristics and biochemical findings at the first presentation as well as follow-up were reviewed. Additionally, the associations of genotypes and phenotypes were explored. Results Forty-one different SLC12A3 mutations were identified in 67 patients with GS, including 11 novel ones, and 5 recurrent ones. 3 families (5. 7% ) had triple SLC12A3 mutations. Typical hypocalciuria and hypomagnesemia were not found in 6(9% ) and 8 (11. 9% )patients, respectively. In addition, male patients had an earlier age of onset and a higher urinary fraction excretion of electrolytes. 2 patients presented with chronic kidney disease, 13 (19. 4% ) with type 2 diabetes, 14 (20. 9% )with impaired glucose tolerance, and 5(7. 5% ) with impaired fasting glucose. Conclusion This study revealed 41 mutations in 67 Chinese patients with GS, including 11 novel variants and 5 high-frequency ones. Fraction excretion of electrolyte in urine may be more sensitive in the evaluation of phenotype compared with those of blood. It is difficult to correct hypokalemia and hypomagnesemia in GS. Patients with GS are at higher risk of the development of diabetes than ordinary people.

Mutation analysis of an adult patient with fructose-1,6-bisphosphatase deficiency in a Chinese family / 中华内分泌代谢杂志

The gene mutations of a patient with fructose-1,6-bisphosphatase (FBPase) deficiency and her parents were analyzed and her clinical manifestations, laboratory tests, and genetic characteristics were reviewed. The molecular analysis of FBP1 gene showed a G residue duplication at base 960 in exon 7(c. 960dupG) in this patient while her parents carried the heterozygous c. 960dupG mutation. The prominent clinical feature of this patient was the benign course of the disease with age. However, acute attack could be triggered by stress, long-time fasting, a large amounts of fructose intake, etc. The typical clinical manifestations were severe lactic acidosis, hypoglycemia, and elevated liver enzymes.

Mutation analysis of an adult patient with fructose-1,6-bisphosphatase deficiency in a Chinese family / 中华内分泌代谢杂志

The gene mutations of a patient with fructose-1,6-bisphosphatase (FBPase) deficiency and her parents were analyzed and her clinical manifestations, laboratory tests, and genetic characteristics were reviewed. The molecular analysis of FBP1 gene showed a G residue duplication at base 960 in exon 7(c. 960dupG) in this patient while her parents carried the heterozygous c. 960dupG mutation. The prominent clinical feature of this patient was the benign course of the disease with age. However, acute attack could be triggered by stress, long-time fasting, a large amounts of fructose intake, etc. The typical clinical manifestations were severe lactic acidosis, hypoglycemia, and elevated liver enzymes.