Journal Article

Genotype–phenotype correlation and natural history study of dysferlinopathy: a single-centre experience from India

Mathew, Susi, Joshi, Aditi, Vengalil, Seena, Ramprasad, Vedam, Chawla, Tanushree, Faruq, Mohammed, Thomas, Abel, Huddar, Akshata, Nalini, Atchayaram, Polavarapu, Kiran, Baskar, Dipti, Anjanappa, Ram Murthy, Geetha, Thenral S, Nashi, ‬Saraswati, Arunachal, Gautham, Padmanabha, Hansashree, Menon, Deepak, Sharma, Pooja, Prathyusha, P. V, Unnikrishnan, Gopikirshnan, Bardhan, Mainak, Uppilli, Bharathram, Thangaraj, Kumarasamy, Preethish-Kumar, Veeramani

2023

Overview

Dysferlinopathies are a group of limb-girdle muscular dystrophies causing significant disability in the young population. There is a need for studies on large cohorts to describe the clinical, genotypic and natural history in our subcontinent. To describe and correlate the clinical, genetic profile and natural history of genetically confirmed dysferlinopathies. We analysed a retrospective cohort of patients with dysferlinopathy from a single quaternary care centre in India. A total of 124 patients with dysferlinopathy were included (40 females). Median age at onset and duration of illness were 21 years (range, 13–50) and 48 months (range, 8–288), respectively. The average follow-up period was 60 months (range, 12–288). Fifty-one percent had LGMD pattern of weakness at onset; 23.4% each had Miyoshi and proximo-distal type while isolated hyperCKemia was noted in 1.6%. About 60% were born to consanguineous parents and 26.6% had family history of similar illness. Twenty-three patients (18.6%) lost ambulation at follow-up; the median time to loss of independent ambulation was 120 months (range, 72–264). Single-nucleotide variants (SNVs) constituted 78.2% of patients; INDELs 14.5% and 7.3% had both SNVs and INDELs. Earlier age at onset was noted with SNVs. There was no correlation between the other clinical parameters and ambulatory status with the genotype. Thirty-seven (45.7%) novel pathogenic/likely pathogenic (P/LP) variants were identified out of a total of 81 variations. The c.3191G > A variant was the most recurrent mutation. Our cohort constitutes a clinically and genetically heterogeneous group of dysferlinopathies. There is no significant correlation between the clinico-genetic profile and the ambulatory status.

• Publisher: Springer Nature B.V
• Subject: Creatine kinase / Genotypes / Natural history / Phenotypes / Serum levels