The Indian Journal of Pediatrics

, Volume 85, Issue 2, pp 87–92 | Cite as

Expanding the Phenotype of the Founder South Asian Mutation in the Nuclear Encoding Mitochondrial RMND1 Gene

  • N. Vinu
  • Ratna D. Puri
  • Kanav Anand
  • Ishwar C. Verma
Original Article



Mitochondrial disorders have a wide variability in the phenotype. A 10-mo-old girl presented with a severe phenotype of multisystem involvement due to an uncommon mitochondrial disease. Mutations in the RMND1 gene of nuclear DNA were identified on next generation sequencing. This mutation results in combined oxidative phosphorylation deficiency −11 (OMIM #614922) of the respiratory chain complex. So far in South Asia, patients of this disorder have been reported only from Pakistan and Bangladesh.


In addition to the features reported in other patients of South Asia with the same mutation at c.1349G>C, index patient from India had hyperaldosteronism, long QT interval but no deafness.


Thus, to conclude, this report emphasizes the diagnostic value of FGF21 assay in this disorder. It extends the phenotype associated with the founder mutation in RMND1 gene in patients from South Asia.


RMND1 Next generation sequencing Combined oxidative phosphorylation Hyperaldosteronism FGF21 Founder mutation 



VN: Participated in the interpretation and writing of the manuscript; RDP, KA, ICV: Participated in the patient management, and interpretation and writing of the manuscript. All the authors approved the final manuscript. RDP will act as guarantor for this paper.

Compliance with Ethical Standards

Conflict of Interest


Source of Funding



  1. 1.
    Ylikallio E, Suomalainen A. Mechanisms of mitochondrial diseases. Ann Med. 2012;44:41–59.CrossRefPubMedGoogle Scholar
  2. 2.
    Taylor RW, Pyle A, Griffin H, et al. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA. 2014;312:68–77.CrossRefPubMedGoogle Scholar
  3. 3.
    Smits P, Antonicka H, van Hasselt PM, et al. Mutation in subdomain G' of mitochondrial elongation factor G1 is associated with combined OXPHOS deficiency in fibroblasts but not in muscle. Eur J Hum Genet. 2011;19:275–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Ng YS, Alston CL, Diodato D, et al. The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease. J Med Genet. 2016;53:768–75.CrossRefPubMedCentralGoogle Scholar
  5. 5.
    Jacobs LJ, de Wert G, Geraedts JP, de Coo IF, Smeets HJ. The transmission of OXPHOS disease and methods to prevent this. Hum Reprod Update. 2006;12:119–36.CrossRefPubMedGoogle Scholar
  6. 6.
    Suomalainen A, Elo JM, Pietilainen KH, et al. FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study. Lancet Neurol. 2011;10:806–18.CrossRefPubMedGoogle Scholar
  7. 7.
    Garcia-Diaz B, Barros MH, Sanna-Cherchi S, et al. Infantile encephaloneuromyopathy and defective mitochondrial translation are due to a homozygous RMND1 mutation. Am J Hum Genet. 2012;91:729–36.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Janer A, Antonicka H, Lalonde E, et al. An RMND1 mutation causes encephalopathy associated with multiple oxidative phosphorylation complex deficiencies and a mitochondrial translation defect. Am J Hum Genet. 2012;91:737–43.Google Scholar
  9. 9.
    Ravn K, Neland M, Wibrand F, Duno M, Ostergaard E. Hearing impairment and renal failure associated with RMND1 mutations. Am J Hum Genet A. 2016;170:142–7.Google Scholar
  10. 10.
    Mallett A, Mordaunt D, Sonawane R, Walker A, Kausman J. RMND1 mutations are associated with autosomal recessive syndromic nephropathy. 51st Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology. 2015; (special issue):41–2.Google Scholar
  11. 11.
    Gupta A, Colmenero I, Ragge NK, et al. Compound heterozygous RMND1 gene variants associated with chronic kidney disease, dilated cardiomyopathy and neurological involvement: a case report. BMC Res Notes. 2016;9:325.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kotecha UH, Movva S, Puri RD, Verma IC. Trichohepatoenteric syndrome: founder mutation in asian Indians. Mol Syndromol. 2012;3:89–93.PubMedPubMedCentralGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2017

Authors and Affiliations

  1. 1.Institute of Medical Genetics and GenomicsSir Ganga Ram HospitalNew DelhiIndia
  2. 2.Division of Pediatric Nephrology, Institute of Child HealthSir Ganga Ram HospitalNew DelhiIndia

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