Clinical features and genetic analysis of two Chinese pedigrees affected with Joubert syndrome.
10.3760/cma.j.cn511374-20220122-00055
- Author:
Dengzhi ZHAO
1
;
Yan CHU
;
Ke YANG
;
Xiaodong HUO
;
Xingxing LEI
;
Yanli YANG
;
Chaoyang ZHANG
;
Hai XIAO
;
Shixiu LIAO
Author Information
1. Henan Provincial People's Hospital, Medical Genetics Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory for Birth Defect Prevention, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan 450003, China. ychslshx@126.com.
- Publication Type:Journal Article
- MeSH:
Female;
Humans;
Pregnancy;
Pedigree;
Cerebellum/abnormalities*;
Abnormalities, Multiple/diagnosis*;
Eye Abnormalities/diagnosis*;
Kidney Diseases, Cystic/diagnosis*;
Phosphoric Monoester Hydrolases/genetics*;
Retina/abnormalities*;
East Asian People;
Mutation
- From:
Chinese Journal of Medical Genetics
2023;40(1):21-25
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome.
METHODS:Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2.
RESULTS:The proband of pedigree 1 was a fetus at 23+5 weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up.
CONCLUSION:The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.
