Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy.

  title={Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy.},
  author={Sarah L. Sawyer and Andy Cheuk-Him Ng and A. Micheil Innes and Justin D. Wagner and David A Dyment and Martine T{\'e}treault and Jacek Majewski and Kym M. Boycott and Robert A. Screaton and Garth A. Nicholson},
  journal={Human molecular genetics},
  volume={24 18},
Multiple symmetric lipomatosis (MSL) is a mitochondrial disorder with impaired brown fat metabolism that has been associated with MERRF mutations in some, but not all, patients. [] Key Result Whole-exome sequencing was performed on the siblings, and a rare, shared homozygous mutation in MFN2 (c.2119C>T: p.R707W) was identified. The mutation was not present in their healthy siblings. In silico programs predict it to be pathogenic, and heterozygous carriers of the MFN2 p.R707W substitution are known to have…

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  • 2021

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Mitochondrial DNA mutations in multiple symmetric lipomatosis

Clinical, electrophysiological morphological, biochemical and molecular genetic findings in 17 MSL patients are summarized, a survey of the literature is given, and there is an association with mitochondrial dysfunction.

Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations.

MFN2 mutations are a frequent cause of CMT2, with variable severity and either dominant or recessive inheritance, and MFN2 gene testing must be a first-line analysis in axonal HMSN irrespective of the mode of inheritance or the severity of the peripheral neuropathy.

Phenotypic heterogeneity of the 8344A>G mtDNA “MERRF” mutation

High clinical heterogeneity showed higher clinical heterogeneity than commonly thought, and MERRF could be better defined as a myoclonic ataxia rather than aMyoclonic epilepsy, as well as some asymptomatic mutation carriers.

Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population.

Severe early-onset axonal neuropathy with homozygous and compound heterozygous MFN2 mutations

Severe early-onset axonal neuropathy due to MFN2 mutations can present as an apparently recessively inherited neuropathy but the minimal phenotype in the parents suggests a semi-dominant mechanism.

Familial multiple symmetric lipomatosis associated with the A8344G mutation of mitochondrial DNA

The proband showed neuromuscular involvement but lacked the typical manifestations of myoclonic epilepsy and ragged-red fibers disease, and the distribution of the mutation was unusual because the proportion of mutated genomes was higher in blood and lipomas than in muscle tissue.

Multiple symmetric lipomas with high levels of mtDNA with the tRNA(Lys) A-->G(8344) mutation as the only manifestation of disease in a carrier of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome.

It is concluded that the lipomas represent clonal growth of adipocytes with a high content of mtDNA with the tRNA(Lys) mutation, which may be either the direct or the indirect cause of pertubation of the maturation process of the adipocytes, leading to an increased risk of lipoma formation.

Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations

It is shown that homooligomeric complexes formed by many Mfn2 disease mutants are nonfunctional for mitochondrial fusion, but wild-type Mfn1 complements mutant Mfn 2 through the formation of heterooligomers, including complexes that form in trans between mitochondria.