The m.7510T>C mutation: Hearing impairment and a complex neurologic phenotype

Area of Science:

• Genetics
• Mitochondrial Biology
• Neurology

Background:

• Mitochondrial DNA mutations lead to diverse clinical outcomes, from hearing impairment to encephalomyopathy.
• The MT-TS1 gene is frequently implicated in hearing loss due to mutations.
• The m.7510T>C mutation in MT-TS1 was previously linked to non-syndromic hearing loss in multiple families.

Purpose of the Study:

• To investigate the clinical, genetic, and histopathological characteristics of the m.7510T>C mutation in a Finnish family.
• To determine the full spectrum of clinical phenotypes associated with the m.7510T>C mutation.

Main Methods:

• Clinical evaluation of family members presenting with various symptoms.
• Genetic analysis to identify and quantify heteroplasmy of the m.7510T>C mutation.
• Muscle biopsy and histopathological examination to assess for mitochondrial myopathy.

Main Results:

• The proband exhibited progressive mitochondrial disease with hearing loss, migraine, epilepsy, ataxia, and cognitive impairment.
• Other family members presented with hearing loss, ataxia, and tremor.
• High mutation heteroplasmy (≥99%) was observed in muscle and blood of affected individuals.
• Muscle histology confirmed mitochondrial myopathy in three family members.

Conclusions:

• The m.7510T>C mutation is associated with sensorineural hearing loss and a broader spectrum of mitochondrial disease.
• Clinical manifestations include neurological symptoms (migraine, epilepsy, ataxia, tremor, cognitive impairment) and mitochondrial myopathy.
• This mutation's phenotypic variability underscores the complex relationship between genotype and phenotype in mitochondrial disorders.