Trivandrum, October 2025 – Dr. Roshan Daniel, one of India’s leading clinical geneticists and Head of the Department of Medical Genetics & Precision Medicine at KIMSHEALTH Hospital, Trivandrum, has co-authored a landmark study in collaboration with Christian Medical College (CMC) Vellore, recently published in the American Journal of Medical Genetics (AJMG Part A).
The publication, titled “A Novel Presentation and Variable Phenotypic Spectrum of Homozygous Start-Loss Variant in LYRM7-Associated Mitochondrial Complex III Deficiency,” reports one of the largest series worldwide describing individuals with a start-loss variant (c.2T>C; p.Met1?) in the LYRM7 gene — a critical gene involved in the assembly of mitochondrial respiratory chain Complex III.
Key Findings:
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Six individuals from South India were identified with the same homozygous start-loss variant in LYRM7, suggesting a possible founder effect in the region.
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The study highlights remarkable clinical variability, with some individuals presenting in early childhood with developmental regression, seizures, and cavitating leukoencephalopathy, while others developed isolated optic neuropathy in adulthood — a novel finding not previously linked to this gene.
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MRI imaging showed characteristic supratentorial white-matter cystic changes, consistent with mitochondrial leukoencephalopathy, helping refine diagnostic radiological markers.
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Despite identical genetic findings, the disease severity and progression varied, emphasizing the role of modifying factors in mitochondrial pathophysiology.
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The authors recommend that LYRM7-associated mitochondrial disease be considered in patients with unexplained leukoencephalopathy, optic atrophy, or poor response to immunotherapy.
Advancing Rare Disease Research in India
The study not only expands the known phenotypic spectrum of LYRM7-related mitochondrial disorders, but also demonstrates the power of collaborative rare disease research between Indian institutions.
Dr. Roshan Daniel, also the Founder of Genetidoc Genetic Clinic and DNA Testing Lab, is a recognized expert in rare genetic and mitochondrial disorders. Through his dual roles at KIMSHEALTH and Genetidoc, he continues to pioneer the integration of advanced genomics, molecular diagnostics, and clinical genetics into patient care.
🔗 Read the full article on PubMed: https://pubmed.ncbi.nlm.nih.gov/40317892/