RESUMO
Objective:To report four male COL4A5 mutation mosaicism patients with X-linked Alport syndrome, and to provide evidence for diagnosis, genetic counseling, and reproduction in the respective families and improve our knowledge of mosaicism in Alport syndrome. Methods:Suspected male mosaic patients for COL4A5 who met the following criteria: clinical diagnosis of Alport syndrome, harbored COL4A5 mutations detected using next generation sequencing or Sanger sequencing, heterozygosity for the mutant and normal COL4A5 alleles in the DNA demonstrated by Sanger sequencing, registered in the on-line registry of hereditary kidney diseases, and admitted to Peking University First Hospital during the period of April 2018 to April 2019 were enrolled. Clinical data and karyotypes were retrospectively analyzed. Genetic DNA isolated from multiple tissues was analyzed for COL4A5 gene mutations by using PCR and Sanger sequencing. Related literatures published in PubMed, CNKI and Wanfang databases were reviewed. Results:Four COL4A5 somatic and germline mosaic male patients with Alport syndrome were included in the study. Patient 1 was characterized by hematuria and proteinuria. His karyotype of peripheral blood was normal. COL4A5 c.3455-1G>A mosaicism was detected in multiple tissues (peripheral blood, saliva and urine). Patient 2 presented with hematuria and microalbuminuria. His karyotype of peripheral blood was normal. COL4A5 c.4994+1G>A mosaicism was detected in multiple tissues (peripheral blood, saliva and skin fibroblasts). Patients 3 showed hematuria without proteinuria. COL4A5 c.3535G>A mosaicism was found in genomic DNA of peripheral blood and hair. Laboratory and physical examinations of patient 4 showed hematuria and normal renal function, without proteinuria, megasoma or small testes. COL4A5 c.3106G>A mosaicism was detected in genomic DNA of skin fibroblasts. Although without karyotype analysis due to unavailable specimens, 47,XXY or 46,XY/47,XXY mosaicism was not considered according to the reproductive history and lack of clinical manifestations of megasoma and small testes in patients 3 and 4. Renal disease in 8 published male cases with mosaicism for COL4A5 was affected by mutant allelic fractions and genotype. Conclusions:Compared with hemizygous males with X-linked Alport syndrome, the renal phenotype of mosaic males was milder, and associated with mutant allelic fractions and mutation type.
RESUMO
Objective To explore the feasibility of establishing such an on_line registry of hereditary kidney diseases in Chinese children. Methods Selecting disease categories,designing input parameters,data quality and secu_rity are key factors of establishing an on_line registry of hereditary kidney diseases including general information,clini_cal data,relevant examinations,genetic testing,medication and follow_up. Results The first on_line,multi_cen_tered registry of children with hereditary kidney diseases in China was established using Java language and MySQL data_base. It contained 1 580 parameters and covered 6 major hereditary kidney diseases including Alport syndrome,protei_nuria related kidney disease,renal tubular disease,renal cystic disease,congenital anomalies of kidney and urinary tract and other hereditary kidney diseases. To date,a total of about 2 200 families from 32 tertiary hospitals have been regis_tered. About 648 families have well_documented follow_up records with a maximum follow_up of 13. 5 years. The registration system has data screening,export and simple statistical functions. The registry system had a clear interface, and was convenient and friendly to use. The input data could be real_time updated,and dedicated personnel was re_sponsible for data review and quality control to ensure security and reliability. Conclusions The on_line registry of children with hereditary kidney diseases not only facilitates standardized management of patients. Moreover,it provides a platform and a good foundation for the establishment and expansion of clinical research cohort.
RESUMO
Objective To observe the effects of mizoribine(MZR)on renal tubular epithelial?mesenchymal transition(EMT)of mice which have been performed unilateral ureteral obstruction(UUO),and study the mechanism of its anti?fibrosis of renal interstitial. Methods A total of 24 CD1 mice were randomly divided into sham group,UUO model group and MZR treatment group,with 8 mice in each group. The day before op?eration,mice of MZR treatment group had been given MZR 10 mg/kg/d lavage,those of sham group and UUO model group had been given equal saline lavage. Fourteen days after the operation ,blood was collected and serum creatinine and blood urea nitrogen were measured;the obstruction kidneys were harvested for section,HE staining and Masson staining were employed to observe the changes of kidney pathological;the expression ofα?SMA and E?Cad in kidney with detected by immunohistochemical and Western blot method. Results Compared with sham group,serum creatinine and blood urea nitrogen of mice in UUO model group and MZR treatment group were significantly elevated ,kidney pathological chang?es and the expression ofα?SMA in renal tissue were increased and that of E?Cad was reduced ,the differences were all statistically significant(P<0.05);compared with UUO model group,mice in MZR treatment group had different degree of improvements in serum creatinine,blood urea ni?trogen and kidney pathological changes ,the expression ofα?SMA in renal tissue was inhibited and that of E?Cad was increases ,and the differences were statistically significant(P<0.05). Conclusion MZR may inhibit the development of renal tubular EMT in UUO mice ,thereby reduce the level of renal tubule interstitial fibrosis and improve renal function.