Clinical features and genetic analysis of a child with acute form of Tyrosinemia type I due to a novel variant of FAH gene.
10.3760/cma.j.cn511379-20211119-00921
- Author:
Qinghua ZHANG
1
;
Chuan ZHANG
;
Yupei WANG
;
Weikai WANG
;
Ruifeng XU
;
Ling HUI
;
Xuan FENG
;
Xing WANG
;
Lei ZHENG
;
Binbo ZHOU
;
Yan JIANG
;
Shengju HAO
Author Information
1. Medical Genetics Center, Gansu Provincial Maternal and Child Health Care Hospital, Lanzhou, Gansu 730050, China. 45251377@qq.com.
- Publication Type:Journal Article
- MeSH:
Female;
Humans;
Gas Chromatography-Mass Spectrometry;
Genetic Testing;
Mutation;
Phenotype;
Prenatal Diagnosis;
Tyrosinemias/genetics*;
Child
- From:
Chinese Journal of Medical Genetics
2023;40(2):171-176
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1).
METHODS:A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing.
RESULTS:The child's clinical features included abdominal distension, hepatomegaly, anemia and tendency of bleeding. By mass spectrometry analysis, her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges. WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C (p.Cys315Arg) compound heterozygous variants of the FAH gene, which were inherited from her father and mother, respectively. Among these, the c.943T>C was unreported previously.
CONCLUSION:Considering her clinical phenotype and result of genetic testing, the child was diagnosed with TYRSN1 (acute type). The compound heterozygous variants of the FAH gene probably underlay the disease in this child. Above finding has further expanded the spectrum of FAH gene variants, and provided a basis for accurate treatment, genetic counseling and prenatal diagnosis for her family.
