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  3. A novel TRMT5 mutation causes a complex inherited neuropathy syndrome: the role of nerve pathology in defining a demyelinating neuropathy.

A novel TRMT5 mutation causes a complex inherited neuropathy syndrome: the role of nerve pathology in defining a demyelinating neuropathy.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Marco-Marin, Clara
  • Serrano-Lorenzo, Pablo
  • Martin, Miguel A.

Grupos

Abstract

AIMS: To present data obtained from three patients belonging to three unrelated families with an infantile onset demyelinating neuropathy associated to somatic and neurodevelopmental delay, and to describe the underlying genetic changes. METHODS: We performed whole-exome sequencing on genomic DNA from the patients and their parents, and reviewed the clinical, muscle and nerve data, the serial neurophysiological studies, brain, and muscle MRIs, as well as the respiratory chain complex activity in the muscle of the three index patients. Computer modelling was used to characterize the new missense variant detected. RESULTS: All three patients had a short stature, delayed motor milestone acquisition, intellectual disability and cerebellar abnormalities associated with a severe demyelinating neuropathy, with distinct morphological features. Despite the proliferation of giant mitochondria, the mitochondrial respiratory chain complex activity in skeletal muscle was normal, except in one patient in whom there was a mild decrease in complex I enzyme activity. All three patients carried the same two compound heterozygous variants of the TRMT5 (tRNA Methyltransferase 5) gene, one known pathogenic frameshift mutation [c.312_315del (p.Ile105Serfs*4)] and a second rare missense change [c.665T>C (p.Ile222Thr)]. TRMT5 is a nuclear-encoded protein involved in the post-transcriptional maturation of mitochondrial tRNA. Computer modelling of the human TRMT5 protein structure suggests that the rare p.Ile222Thr mutation could affect the stability of tRNA binding. CONCLUSIONS: Our study expands the phenotype of mitochondrial disorders caused by TRTM5 mutations and defines a new form of recessive demyelinating peripheral neuropathy.

© 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Datos de la publicación

ISSN/ISSNe:
0305-1846, 1365-2990

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY  WILEY

Tipo:
Article
Páginas:
-
PubMed:
35342985
Factor de Impacto:
1,889 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 11

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Keywords

  • TRMT5; inherited neuropathy; mitochondrial disorders; mitochondrial neuropathies

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