Infantile Onset Encephalomyopathy, Heart Block, and Sensorineural Hearing Loss: RMND1-Associated Mitochondrial DiseaseFunding This study was supported by a grant from the Indian Council of Medical Research to B.P.S. (grant no.: 54/9/2012-HUM-BMS).
Mutations in RMND1 (required for mitotic division-1) has been associated with infantile onset mitochondrial disease and combined oxidation phosphorylation deficiency. This report describes a girl child of Indian origin with RMND1-associated mitochondrial disease. This 13-month-old girl, born to consanguineous parents presented with gradual loss of acquired milestones and recurrent vomiting from 5 months of age. She experienced failure to thrive, profound hypotonia, areflexia, and sensorineural deafness. Evaluation showed elevated serum lactate and complete heart block. Audiological evaluation done at 6 and 13 months of age revealed bilateral A type tympanogram, bilateral absent stapedial reflexes, absent otoacoustic emissions (OAE), and absent brainstem auditory evoked responses suggestive of bilateral profound sensorineural hearing loss. Muscle biopsy revealed evidence of ragged red fibers, ragged blue fibers, and Cytochrome coxidase (COX) deficient fibers on histochemistry and multiple complex deficiency on spectrophotometry. Exome sequencing revealed homozygous stop-loss variation, c.1349G > C, in exon 12 of RMDN1 resulting in substitution of amino acid serine for stop codon at position 450 and subsequent elongation of the protein by 31 amino acids (p.Ter450SerextTer31) which was verified by Sanger's sequencing. This report further strengthens the phenotype genotype correlations in RMND1-associated mitochondrial disease, especially the occurrence of the reported variation in South Asian patients. In addition, familiarity with the phenotype might help the physician to do targeted metabolic testing and facilitate appropriate early interventions.
B.P.S. and A.B.T. contributed in conceptualization and designing, as well as acquisition, analysis, and interpretation of data. M.N. performed the literature search and wrote the manuscript. A.B.T., B.P.S., M.N., S.C., and S.S. performed as a clinical team involved in the evaluation, management, and follow-up of the patient. N.G. was involved in the acquisition and interpretation of histopathological data. J.N.J.P. contributed in acquisition and interpretation of respiratory chain assays. S.C. and P.G. performed interpretation of genetic data. V.P.V. contributed with acquisition and interpretation of audiological findings. All authors reviewed and approved the final manuscript.
Eingereicht: 31. Dezember 2019
Angenommen: 19. April 2020
26. Mai 2020 (online)
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