Clinical phenotype and genetic characteristics of two families with tuberous sclerosis
10.3760/cma.j.cn115354-20200429-00322
- VernacularTitle:结节性硬化症二家系的临床表型及遗传学特点分析
- Author:
Daoqi MEI
1
;
Shiyue MEI
;
Xiaona WANG
;
Xiaoyi CHEN
;
Yuan WANG
;
Guohong CHEN
;
Yaodong ZHANG
;
Ying WANG
;
Shijie DONG
Author Information
1. 郑州大学附属儿童医院 河南省儿童医院 郑州儿童医院东区神经内科，郑州 450018
- Keywords:
Tuberous sclerosis;
Gene mutation;
Epilepsy
- From:
Chinese Journal of Neuromedicine
2020;19(10):1040-1043
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical features and genetic etiology of tuberous sclerosis (TSC).Methods:A retrospective analysis was carried out to identify the clinical features and auxiliary examination reults of TSC patients in 2 pedigrees admitted to our hospital from January 2018 to April 2018. Whole exome sequencing was performed in peripheral blood samples from these patients and the mutations in their parents were validated by Sanger sequencing.Results:The two probands were a one-year and 7-month old girl and a 2-year and 4-month old boy. They were all normal at birth and had epileptic seizures at preschool age. The elder sister, younger sister and mother of the probands showed abnormal skin and no seizures, and the father had normal phenotype. Physical examination showed normal mental and motor development, facial angiofibroma and depigmentation spots on the skin, knots and shark-like spots on part of the skin, and multiple intracranial calcification shadows on head CT; MR imaging revealed multiple abnormal signals under the parenchymal cortex and bilateral lateral ventricles. The proband (1) and her sister carried heterozygous missense mutation c.5024 c >T(p.pro1675leu) in TSC2 gene; ultrasound of heart, liver and kidney showed presence of hamartoma and cystic scotoma in renal parenchyma. The proband (2) and his younger sister carried heterozygosous splicing variation c. 737+1(IVS8)G>A in TSC1 gene, inherited from his mother; the head CT of younger sister was normal, and there was no hamartoma in the younger sister and the mother's internal organs. Conclusions:TSC is characterized by epileptic seizures and abnormal skin changes in preschool age. It may involve multiple hamartomas of skull, heart, liver, kidney, or other internal organs. The mutation frequency of TSC2 gene is higher than that of TSC1 gene, and the clinical phenotype is severe.
