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Biallelic Mutations in DNM1L are Associated with a Slowly Progressive Infantile Encephalopathy
Author(s) -
Nasca Alessia,
Legati Andrea,
Baruffini Enrico,
Nolli Cecilia,
Moroni Isabella,
Ardissone Anna,
Goffrini Paola,
Ghezzi Daniele
Publication year - 2016
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23033
Subject(s) - biology , mitochondrial fission , mitochondrion , genetics , missense mutation , peroxisome , mutation , dynamin , microbiology and biotechnology , gene , endocytosis , cell
Mitochondria are highly dynamic organelles, undergoing continuous fission and fusion, and mitochondrial dynamics is important for several cellular functions. DNM1L is the most important mediator of mitochondrial fission, with a role also in peroxisome division. Few reports of patients with genetic defects in DNM1L have been published, most of them describing de novo dominant mutations. We identified compound heterozygous DNM1L variants in two brothers presenting with an infantile slowly progressive neurological impairment. One variant was a frame‐shift mutation, the other was a missense change, the pathogenicity of which was validated in a yeast model. Fluorescence microscopy revealed abnormally elongated mitochondria and aberrant peroxisomes in mutant fibroblasts, indicating impaired fission of these organelles. In conclusion, we described a recessive disease caused by DNM1L mutations, with a clinical phenotype resembling mitochondrial disorders but without any biochemical features typical of these syndromes (lactic acidosis, respiratory chain complex deficiency) or indicating a peroxisomal disorder.