Genetic analysis of a Chinese pedigree affected with atypical Charcot-Marie-Tooth disease type 1A due to duplication of PMP22 gene
10.3760/cma.j.cn511374-20230214-00072
- VernacularTitle:PMP22基因重复致非典型腓骨肌萎缩症1A型一个家系的遗传学分析
- Author:
Ling YAO
1
;
Min LI
;
Lijuan LIU
;
Zhirong FAN
;
Yu′nan JIA
;
Jing WANG
;
Fang DU
Author Information
1. 空军军医大学附属西京医院神经内科，西安 710032
- Keywords:
Muscular Atrophy;
Charcot-Marie-Tooth disease type 1A;
Peripheral myelin protein 22;
Neuropathic pain;
Pes arcuatus
- From:
Chinese Journal of Medical Genetics
2024;41(4):443-449
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical manifestations and genetic basis for a Chinese pedigree affected with atypical Charcot-Marie-Tooth disease type 1 A (CMT1A).Methods:A patient admitted to the Department of Neurology, Xijing Hospital Affiliated to Air Force Medical University in June 2022 was selected as the study subject. Clinical data of the patient was collected, and 17 family members from four generations of this pedigree were traced based on pes arcuatus and atypical clinical symptoms. Neuroultrasound and genetic testing were carried out on available family members. Whole exome sequencing and multiple ligation-dependent probe amplification assay were carried out for the proband and some of the affected members of the pedigree.Results:The proband, a 15-year-old male, had presented with paroxystic limb pain with weakness, accompanied by pes cavus and hypertrophy of gastrocnemius muscles, without stork leg sign caused by muscles atrophy in the distal lower extremities. MRI has revealed no sign of fat infiltration in the muscles of both legs. Nerve conduction examination had indicated damages of the sensory and motor nerves of the limbs, mainly with demyelinating changes. Seven members of the pedigree had pes arcuatus, including 5 presenting with paroxysmal neuropathic pain and myasthenia in the limbs, whilst 2 were without any clinical symptoms. Neurosonography of the proband, his brother, father and aunt showed thickened peripheral nerves of the extremities with unclear bundle structure. Genetic analysis revealed a large repeat encompassing exons 1 to 5 of the PMP22 gene and flanking regions (chr17: 15133768_15502298) in some of the affected members, which was predicted to be pathogenic. Conclusion:The duplication of PMP22 gene was considered to be pathogenic for this CMT1A pedigree.
