Clinical, Pathological and Genetic Analysis of Alport Syndrome in Children
10.12376/j.issn.2097-0501.2022.03.006
- VernacularTitle:儿童Alport综合征的临床、病理及基因分析
- Author:
Jie NI
1
;
Zhi CHEN
1
;
Chen LING
1
;
Xiaorong LIU
1
Author Information
1. Department 1 of Nephrology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
- Publication Type:Journal Article
- Keywords:
Alport syndrome;
collagen Ⅳ;
genotype-phenotype correlation;
next-genation sequencing
- From:
JOURNAL OF RARE DISEASES
2022;1(3):259-267
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the phenotype-genotype correlation of Alport syndrome in children. Methods Retrospectively analyze the clinical and pathological features of 55 patients with Alport syndrome with COL4A mutations detected by second-generation sequencing, who were treated at Beijing Children's Hospital from January 2016 to December 2020. Results A total of 55 children with Alport syndrome were included. All cases had hematuria, including 31 cases (56.4%) with gross hematuria and 24 cases (43.6%) with microscopic hematuria. A total of 39 (70.9%) patients also had proteinuria. Extrarenal manifestations were pres- ent in 12 patients (21.8%). 36(65.4%) patients had a family history of Alport syndrome. 32 patients underwent pathological examination and 23 of them had the specific pathological changes of Alport syndrome. In 55 cases, 36 (65.4%) were diagnosed as X-linked Alport syndrome, 5(9.1%) were diagnosed as autosomal recessive Alport syndrome, 10(18.2%) were diagnosed as autosomal dominate Alport syndrome, and 4(7.3%) were diagnosed as digenic Alport syndrome. Missense mutations in COL4A genes accounted for 62.5%, 67.5% of missense mutations resulted in glycine substitution. There were statistical significances in proteinuria degree and hearing loss between male and female patients with XLAS (P < 0.05) as well as statistical significance in the degree of proteinuria between autosomal recessive Alport syndrome and autosomal dominate Alport syndrome (P=0.044), and there was critical statistical significance in the age of onset. There was statistical significance in hearing loss between children with renal impairment and children with normal renal function (P=0.001). Conclusions Most of the pathogenic variants in COL4A genes that cause Alport syndrome result in glycine substitutions. The degree of proteinuria and hearing loss of males with XLAS were greater than those of females. The degree of proteinuria in autosomal recessive Alport syndrome was greater than that of children with autosomal dominate Alport syndrome, and the age of onset was earlier than that of autosomal dominate Alport syndrome. Renal manifestation was more severe in children with hearing loss. The early clinical manifestations of Alport syndrome are diverse and pathological manifestations may be atypical. The application of next-generation sequencing can reduce misdiagnosises of Alport syndrome.
