Analysis of ALMS1 gene variants in seven patients with Alström syndrome.
10.3760/cma.j.cn511374-20200115-00033
- Author:
Yu DING
1
,
2
;
Qianwen ZHANG
;
Yingzhong HE
;
Lei ZHANG
;
Niu LI
;
Guoying CHANG
;
Yao CHEN
;
Jian WANG
;
Jinjin WU
;
Lijun FU
;
Xiumin WANG
Author Information
1. Department of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China. wangxiumin@scmc.com.cn
2. fulijun@scmc.com.cn.
- Publication Type:Journal Article
- MeSH:
Alstrom Syndrome/genetics*;
Cell Cycle Proteins/genetics*;
Humans;
Mutation;
Pedigree;
Whole Exome Sequencing
- From:
Chinese Journal of Medical Genetics
2021;38(2):112-116
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis for 7 patients with Alström syndrome.
METHODS:DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.
RESULTS:Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4).
CONCLUSION:ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.