Current Status, Opportunities and Challenges of Rare Endocrine and Metabolic Diseases / 罕见病研究

The rare endocrine and metabolic diseases, due to their varieties, face many challenges in the study of clinical diagnosis, pathogenesis, and treatment. In the past a couple of years, the research on rare endocrine and metabolic diseases has been gradually improved. The diagnosis has made great progress. The research into molecular mechanism of rare endocrine and metabolic diseases has significantly advanced. The effort in exploring the breakthroughs and progress in therapeutic methods based on the pathogenesis of the diseases has also made. This article provides a brief overview of the current status of research into diagnosis, mechanism, and treatment of rare endocrine and metabolic diseases. In addition, the article points out the problems and challenges and proposes future possibilities.

Identification and functional analysis of combined oxidative phosphorylation deficiency 28 gene mutation / 中华内科杂志

Objective:To report a case of combined oxidative phosphorylation deficiency 28 (COXPD28) in China, identified the pathogenic mutation and explored the pathogenic mechanism preliminarily.Methods:The clinical characteristics of a patient with COXPD28 were retrospectively analyzed and the pathogenic mutations were identified by mitochondrial gene sequencing and whole exome sequencing. The wild-type and mutant plasmids of pathogenic genes were constructed, and effect of mutation on protein expression by quantitative real-time PCR (qPCR) and Western blot were evaluated. Statistical methods mainly used one-way ANOVA and LSD test.Results:A 21 year old female patient presented with lactic acid poisoning due to repeated chest distress and wheezing since childhood. The sequencing of the whole exon group gene found that solute carrier family 25 member 26 (SLC25A26) gene had a compound heterozygous mutation (c.34G>C, p.A12P; c.197C>A, p.A66E), which was the first report in China. In vitro function test showed that the expression levels of SLC25A26 mRNA and S-adenosylmethionine carrier (SAMC) protein in cells transfected with SLC25A26 mutant plasmid were significantly lower than those transfected with wild type plasmid. The p.A66E mutant plasmid reduced the expression level of SLC25A26 mRNA and SAMC protein to 6% and 26% of wild type plasmids respectively (both P<0.001), while p.A12P mutant plasmid decreased to 62% and 82% of wild type plasmids respectively ( P<0.001, P=0.044). When the double mutant (p.A66E+p.A12P) plasmids were co-transfected, the expression levels of SLC25A26 mRNA and SAMC protein decreased to 47% and 57% of the wild type plasmids, respectively ( P<0.001, P=0.001). Conclusion:The pathogenic mutation gene of this patient with COXPD28 is SLC25A26 gene mutation (p.A66E, p.A12P), which causes the decrease of SLC25A26 expression level, mitochondrial oxidative phosphorylation dysfunction, and induces COXPD28.

Research process in molecular genetics of Gitelman syndrome / 中华内分泌代谢杂志

Gitelman syndrome(GS) is an autosomal recessive genetic disease caused by mutations in the SLC12A3 gene located in chromosome 16q13. The incidence of GS is 1-10∶40 000. SLC12A3 encodes thiazide-sensitive sodium-chloride cotransporters(NCC) which play key roles in Na + and Cl - reabsorption. GS is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesaemia and low urinary calcium excretion. There are some correlations between genotypes and phenotypes. In previous studies, more than 500 mutations have been identified and some of them have been functionally analyzed. We review genetic mutations and functional studies related to GS as well as the relationship between genotypes and phenotypes, and summarize the research process in molecular genetics of GS.

Exploration of the dynamic responses of Sertoli cells to depletion of spermatogonial stem cells in mouse testis / 中国实验动物学报

Objective To explore the dynamic responses of Sertoli cells to depletion of spermatogonial stem cells by busulfan.Methods After intraperitoneal injection of 15, 30 or 44 mg/kg busulfan to mice, the spermatogenesis and the expression of GDNF, PLZF, Nanog and GFRɑ1 mRNA were assessed by real-time quantitative PCR at 5 and 28 days after the busulfan treatment.Results Glial cell line-derived neutrophic factor ( GDNF ) was significantly increased and showed a dose-dependent trend at 5 days after busulfan treatment, but no significant difference was seen in the expression of promyelocytic leukemia zinc finger(PLZF) and GDNF family receptorα-1(GFRα1).The testicular histology also appeared no significant difference at 5 days after busulfan treatment.At 28 days after busulfan treatment, the relative expression lev-els of GDNF, PLZF, Nanog and GFRɑ1 mRNA were drastically increased.Morphological observation showed that spermat-ogenesis damages became even more severe as the busulfan dose increased.Conclusions Sertoli cell response to the de-pletion of spermatogonia occurs as early as the fifth day after busulfan treatment.Production of GDNF in Sertoli cells shows a compensatory increase, which may stimulate spermatogonial stem cells to accelerate their self-renewal, reflected by the enhancing expression of Nanog and PLZF, and ultimately promote the restoration of spermatogenesis.