Portal de Periódicos da CAPES

Artigo Produção Nacional Revisado por pares

BIBTEX RIS

CMT AND NEUROGENIC DISEASE

2018; Elsevier BV; Volume: 28; Linguagem: Inglês

10.1016/j.nmd.2018.06.389

1873-2364

Eduardo de Paula Estephan, Pedro Henrique Martins Arruda Sampaio, Fausto Rodrigues De Souza, Maria Sheila Guimarães Rocha, Edmar Zanoteli, Wilson Marques,

Neurological diseases and metabolism

Pathogenic variants in the GARS gene cause peripheral nerve degeneration and are associated with Charcot-Marie-Tooth (CMT) disease type 2D and distal hereditary motor neuropathies (dHMN) type 5A. These are allelic diseases and familial variants may present either CMT2D or dHMN phenotypes, and are associated with axonal features on electrophysiology studies. We describe a 11-year-old male from Brazil, with complaints of progressive weakness, difficult walking and distal decreased sensation, since he was 8 years old. On examination, distal muscle wasting, decreased deep tendon reflexes and pes planus were also noticed. Nerve conduction studies revealed upper limbs compound muscle action potentials (CMAPs) with reduced amplitudes, moderately increased distal latencies, reduced conduction velocities (averaging from 25.5 to 32.9 m/s) and slightly increased duration on the left ulnar nerve. CMAPs were not obtained on lower limbs. Sensory nerve action potentials were reduced in amplitude and with normal conduction velocity and latencies on all limbs, while electromyography revealed signs of chronic denervation in distal muscles. The findings were classified as an intermediate electrophysiological pattern. Genetic panel for hereditary neuropathies disclosed a novel missense variant (c.794C>A; p.Ser265Tyr) on exon 7 of GARS gene. The variant is not present in the population databases (EXAC, GNoMAD, EVS), it is located in a very conserved residue and is predicted to be damaging according MetaSVM and MetaLR. His mother and his maternal half-sister both had distal limb weakness and electrophysiological evidence of distal chronic denervation affecting upper and lower limbs, compatible with dHMN type 5. Although intermediate pattern CMT is commonly associated with mutations of some genes, this is the first report of pathogenic variant on GARS leading to such presentation, what indicates an expansion of the phenotype-genotype correlations related to this gene.