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Published on: June 9, 2021
Phenotype Genotype Characterization of FKRP-related Muscular Dystrophy among Indian Patients
Gopikrishnan Unnikrishnan1, Kiran Polavarapu1,2, Mainak Bardhan1,3
1Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India.
Background:
The phenotypic spectrum of Fukutin-related protein (FKRP) mutations is highly variable and comprises of limb girdle muscular dystrophy (LGMD) R9 (previously LGMD 2I) and FKRP related congenital muscular dystrophies.
Objective:
To identify the distinct genotype phenotype pattern in Indian patients with FKRP gene mutations.
Methods:
We retrospectively reviewed the case files of patients with muscular dystrophy having a genetically confirmed FKRP mutation. All patients had undergone genetic testing using next-generation sequencing.
Results:
Our patients included five males and four females presenting between 1.5 years and seven years of age (median age - 3 years). The initial symptom was a delayed acquisition of gross motor developmental milestones in seven patients and recurrent falls and poor sucking in one patient each. Two patients had a language delay, with both having abnormalities on the brain MRI. Macroglossia, scapular winging, and facial weakness were noted in one, three and four patients respectively. Calf muscle hypertrophy was seen in eight patients and ankle contractures in six. At the last follow-up, three patients had lost ambulation (median age - 7 years; range 6.5-9 years) and three patients had not attained independent ambulation. Creatine kinase levels ranged between 2793 and 32,396 U/L (mean 12,120 U/L). A common mutation - c.1343C>T was noted in 5 patients in our cohort. Additionally, four novel mutations were identified. Overall, six patients had an LGMD R9 phenotype, and three had a congenital muscular dystrophy phenotype.
Conclusion:
Patients with FKRP mutations can have varied presentations. A Duchenne-like phenotype was the most commonly encountered pattern in our cohort, with c.1343C>T being the most common mutation.
Insights
Fukutin-related protein (FKRP) gene mutations cause variable muscular dystrophies in Indian patients. A Duchenne-like presentation and the c.1343C>T mutation were most common in this cohort.
Area of Science:
- Genetics
- Neuromuscular Disorders
- Molecular Biology
Background:
- Fukutin-related protein (FKRP) mutations present a wide spectrum of phenotypes, including limb girdle muscular dystrophy R9 and FKRP-related congenital muscular dystrophies.
- Understanding the genotype-phenotype correlation is crucial for diagnosing and managing these rare genetic disorders.
Purpose of the Study:
- To delineate the specific genotype-phenotype patterns associated with FKRP gene mutations in the Indian population.
- To identify common and novel FKRP mutations within this cohort.
Main Methods:
- Retrospective review of case files for patients with genetically confirmed FKRP mutations.
- Genetic analysis performed using next-generation sequencing to identify mutation types.
Main Results:
- The study included nine patients (5 males, 4 females) presenting with symptoms between 1.5 and 7 years of age.
- Common findings included delayed gross motor milestones, calf muscle hypertrophy, and facial weakness. Six patients exhibited an LGMD R9 phenotype, while three had a congenital muscular dystrophy phenotype.
- The c.1343C>T mutation was identified in five patients, and four novel mutations were discovered.
Conclusions:
- FKRP mutations lead to diverse clinical presentations, often mimicking a Duchenne-like muscular dystrophy phenotype.
- The c.1343C>T mutation is a prevalent mutation in Indian patients with FKRP-related muscular dystrophies.
