Genetic analysis of a child with D bifunctional protein deficiency born to a consanguineous pedigree.
10.3760/cma.j.cn511374-20220921-00638
- Author:
Lijia LI
1
;
Qingyi LONG
;
Xiaomei WEN
;
Xue LI
;
Yang TIAN
;
Yecheng FENG
;
Qiuyue ZHANG
Author Information
1. Department of Pediatrics, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, China. zhangqy6699@163.com.
- Publication Type:Journal Article
- MeSH:
Female;
Humans;
Pedigree;
Muscle Hypotonia;
Hearing Loss, Sensorineural;
Protein Deficiency;
Mutation
- From:
Chinese Journal of Medical Genetics
2023;40(7):871-875
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic etiology of a child with D bifunctional protein deficiency (DBPD) born to a consanguineous pedigree.
METHODS:A child with DBPD who was admitted to the First Affiliated Hospital of Hainan Medical College on January 6, 2022 due to hypotonia and global developmental delay was selected as the study subject. Clinical data of her pedigree members were collected. Peripheral blood samples of the child, her parents and elder sisters were collected and subjected to whole exome sequencing. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.
RESULTS:The child, a 2-year-and-9-month-old female, had featured hypotonia, growth retardation, unstable head lift, and sensorineural deafness. Serum long-chain fatty acids were elevated, and auditory brainstem evoked potentials had failed to elicit V waves in both ears with 90 dBnHL stimulation. Brain MRI revealed thinning of corpus callosum and white matter hypoplasia. The child's parents were secondary cousins. Their elder daughter had a normal phenotype and no clinical symptoms related to DBPD. Elder son had frequent convulsions, hypotonia and feeding difficulties after birth, and had died one and a half month later. Genetic testing revealed that the child had harbored homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene, for which both of her parents and elder sisters were carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.483G>T (p.Gln161His) was rated as a pathogenic variant (PM1+PM2_Supporting+PP1+PP3+PP4).
CONCLUSION:The homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene caused by the consanguineous marriage probably underlay the DBPD in this child.
