Genotypic And Phenotypic Features of Patients with GJB1 Mutations: Single Center Experience
Fatma Yesim Parman1, Arman Cakar1, Ayse Candayan2, Hacer Durmus3, Esra Battaloglu2
1Neuromuscular Unit, Neurology Department, Istanbul Faculty of Medicine, Istanbul University, 2Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey, 3Department of Neurology, Istanbul Faculty of Medicine
Objective:
To describe the clinical and genetic characteristics of patients with GJB1 mutations in Turkey.
Background:
GJB1 mutations are the most common cause of X-linked Charcot-Marie-Tooth (CMT) disease. Typical manifestation includes distal muscle weakness and atrophy in the lower limbs. On the other hand, additional clinical features, such as stroke-like episodes, vocal cord paralysis, and hearing loss, can be observed.
Design/Methods:
Herein, we evaluated the clinical and genetic features of 29 patients from 23 unrelated families with GJB1 mutation at the Neuromuscular Unit of the Istanbul Faculty of Medicine, Istanbul University.
Results:
Eight patients were female. The mean age of onset was 19.0 ± 12.0 (between 3 and 53 years). Females (27.3 ± 13.2) had later disease onset than males (15.4 ± 11.4). The most common presenting symptom was distal muscle weakness and foot deformities (21 patients), followed by foot pain (4 patients) and hand tremor (3 patients). Family history was absent in six patients. Two patients had immunosuppressive treatment for a misdiagnosis of inflammatory neuropathy. In neurological examination, all but two female patients had distal weakness in the lower extremities, and 24 had upper extremity weakness. The most frequent skeletal deformity was pes cavus (25 patients), followed by hammer toes (16 patients). Nine patients had hand tremor, and one had vocal cord paralysis. One patient had a history of stroke-like episodes, and one had multiple-sclerosis like cranial and spinal cord MRI lesions. In a mean disease duration of 22.5 ± 14.6 years all patients were ambulatory. The mean median motor nerve conduction velocity was 36.5 ± 8.2, consistent with intermediate-type CMT disease. Eighteen different mutations were identified in the GJB1 gene.
Conclusions:
Our patients exhibited diverse phenotypic features regarding the disease onset and additional symptoms. Moreover, genotypic features were also heterogeneous, considering the identified mutations were scattered throughout the gene.