Dados do Trabalho

Título

Distal hereditary motor neuropathy: clinical and molecular characterization of a Brazilian population

Resumo

Introduction: The distal hereditary motor neuropathy (dHMN) is a rare form of hereditary neuropathy presenting with a length-dependent motor / predominant motor neuropathy. Additional features as upper motor neuron signs (UMN), respiratory distress, vocal cord involvement may be seen, and together with the inheritance pattern are routinely used for clinical classification. Objectives: To describe the clinical and neurogenetic spectrum of 127 dHMN proband / familie’s diagnosed in reference centre for neuromuscular disorders. Methods: 148 patients from 127 families were included (85 males; mean age 33.7y, range 2-78y). Cases were genetically investigated using next-generation sequencing technics - targeted panel and / or WES. WES was performed in 25 probands. Target panel with 27 genes (AAAS, AARS, BICD2, BSCL2, DCTN1, DYNC1H1, DYNC1H1, FBLN5, FBXO38, GARS, GBE1, HINT1, HSPB1, HSPB3, HSPB8, IGHMBP2, KIF1A, LAS1L, MYH14, PLEKHG5, REEP1, SETX, SLC52A1, SLC52A2, SLC52A3, TRPV4, VRK1) Sanger sequencing was performed for segregation analysis. Results: The inheritance pattern observed was autosomal recessive in 20, dominant in 18 and sporadic in the remaining cases. Ten cases had also UMN signs, 19 had some proximal involvement, 6 had upper limb predominance and 1 had vocal cord involvement. A class 4 or 5 variant was identified in 26% and a VUS in 20% of proband / families. BSCL2 and DNAJB2 were the most frequent cause dHMN in our cohort, another 13 genes have one or two proband. Conclusion: Distal hereditary motor neuropathies encompass a rare neuropathy group. Several causative genes have been identified in the Brazilian cohort, but only a few were found in more than one proband/family. The spectrum of dHMN genes differs considerably between populations. We did not found any predominant causative gene. Additional studies are needed to better determine the genetic profile of our population. It is expected that additional testes for the cases underwent the panel analysis may increase our positivity rate and may give a more accurate genetic picture from our cases.

Palavras Chave

dHMN, hereditary neuropathy, WES,NGS

Área

Neurogenética