Analysis of the clinical phenotype and tripeptidyl peptidase-1 gene mutation in a family with type 2 neuronal ceroid lipofuscinosis
10.3760/cma.j.cn113694-20200314-00176
- VernacularTitle:神经元蜡样质脂褐质沉积症2型一家系临床表型及三肽基肽酶-1基因突变分析
- Author:
Daoqi MEI
1
;
Shiyue MEI
;
Yuan WANG
;
Ying WANG
;
Xiaoyi CHEN
;
Guohong CHEN
;
Xiaona WANG
;
Yaodong ZHANG
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 450018
- From:
Chinese Journal of Neurology
2020;53(10):777-783
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical phenotype and tripeptidyl peptidase-1 (TPP1) gene mutation characteristics in a family with type 2 neuronal ceroid lipofuscinosis (CLN2) confirmed by second generation sequencing. Methods:The clinical data of a family with CLN2 from the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University in June 2018 were collected. The proband was confirmed by using the whole-exome sequencing and the Sanger test of the first generation was used in the family members, and the mutation characteristics of TPP1 gene were analyzed, and the clinical features were summarized.Results:The proband is a three-year- and nine-month-old girl, presented with generalized tonic-clonic seizures, normal mental function, mild backward development of language and movement. The ophthalmic examination showed binocular ametropia, normal visual acuity, and no macular degeneration. Cranial magnetic resonance imaging (MRI) showed widening of the subarachnoid space in the frontotemporal region, deepening of the sulci, and cerebellar atrophy. There were two heterozygous mutations in the TPP1 gene, from her parents with normal phenotypes respectively. The c. 1449-1450insG (p.I484Dfs*7) mutation comes from her father, which is an unreported heterozygous mutation of code-shifting, whereas the c.1417G>A(p.G473R) mutation comes from her mother, which is a known missense mutation, consistent with the characteristic of CLN2 complex heterozygous mutation. The proband′s elder brother, whose first symptom was myoclonic seizure at the age of three, and now he is seven years old with progressive visual impairment and regression of intellectual, motor and cognitive functions. The ophthalmic examination showed retinal degeneration, and the cranial MRI showed whole-brain atrophy with obvious cerebellar atrophy. The pathogenic gene of TPP1 and the complex heterozygous mutation site were consistent with the proband. Now the proband′s younger brother is 2-year- and 10-month-old, whose phenotype is normal, with a single heterozygous mutation of c.1417G>A (p.G473R), which comes from their mother, and the parents of the proband have no clinical phenotype. Conclusions:CLN2 is a rare lysosomal storage disorder that is characterized by seizures, progressive mental and motor deterioration, loss of vision and brain atrophy on MRI, binocular macular degeneration. TPP1 complex heterozygous mutation c. 1449-1450insG(p.I484Dfs*7) and c.1417G>A(p.G473R) is the genetic cause of this case.
