Clinical characteristics and genetic analysis of a case with adult neuronal ceroid lipofuscinosis type 7 due to variant of MFSD8 gene.
10.3760/cma.j.cn511374-20220806-00527
- VernacularTitle:MFSD8变异所致的成人起病的神经元蜡样脂褐质沉积症7型患者1例的临床特征及遗传学分析
- Author:
Shuang HE
1
;
Shuai CHEN
;
Yue PENG
;
Xiaorui FAN
;
Shujian LI
;
Jiewen ZHANG
Author Information
1. Department of Neurology, Henan Provincial People's hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China. lsjdoctor@126.com.
- Publication Type:Journal Article
- MeSH:
Male;
Female;
Humans;
Membrane Transport Proteins/genetics*;
Neuronal Ceroid-Lipofuscinoses/diagnosis*;
Retrospective Studies;
Atrophy;
Mutation
- From:
Chinese Journal of Medical Genetics
2023;40(4):395-401
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the clinical characteristics and genetic variants in a patient with adult ceroid lipofuscinosis neuronal type 7 (ACLN7).
METHODS:A female patient diagnosed with ACLN7 in Henan Provincial People's Hospital in June 2021 was selected as the study subject. Clinical data, auxiliary examination and result of genetic testing were retrospectively analyzed.
RESULTS:The patient, a 39-year-old female, has mainly presented progressive visual loss, epilepsy, cerebellar ataxia and mild cognitive decline. Neuroimaging analysis has revealed generalized brain atrophy, prominently cerebellum. Fundus photography has revealed retinitis pigmentosa. Ultrastructural skin examination has revealed granular lipofuscin deposits in the periglandular interstitial cells. Whole exome sequencing revealed that she has harbored compound heterozygous variants of the MSFD8 gene, namely c.1444C>T (p.R482*) and c.104G>A (p.R35Q). Among these, c.1444C>T (p.R482*) was a well established pathogenic variant, while c.104G>A (p.R35Q) was a missense variant unreported previously. Sanger sequencing confirmed that the daughter, son and elder brother of the proband have respectively carried heterozygous c.1444C>T (p.R482*), c.104G>A (p.R35Q), and c.104G>A (p.R35Q) variants of the same gene. The family has therefore fit with the autosomal recessive inheritance pattern of the CLN7.
CONCLUSION:Compared with previously reported cases, this patient has the latest onset of the disease with a non-lethal phenotype. Her clinical features have involved multiple systems. Cerebellar atrophy and fundus photography may be indicative of the diagnosis. The c.1444C>T (p.R482*) and c.104G>A (p.R35Q) compound heterozygous variants of the MFSD8 gene probably underlay the pathogenesis in this patient.
