SIGMAR1 gene mutation causing Distal Hereditary Motor Neuropathy in a Portuguese family

Luciano Almendra 1, Francisco Laranjeira 2 , Ana Fernández-Marmiesse 3, Luís Negrão 1

1 Consulta de Doenças Neuromusculares, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal; 2 Centro de Genética Clínica, Centro Hospitalar do Porto; 3 Unidad de Diagnóstico y Tratamiento de Enfermidades Metabolicas Congénitas (UDyTEMC), Hospital Clínico Universitário de Santiago de Compostela

SIGMAR1 gene encodes a non-opioid endoplasmic reticulum (ER) protein which is involved in a large diversity of cell functions and is expressed ubiquitously in both central and peripheral nervous systems. Alterations of its normal function may contribute to two different phenotypes: juvenile amyotrophic lateral sclerosis (ALS 16) and distal hereditary motor neuropathies (dHMN). We present the case of a female patient, of 37-years-old, with distal muscle weakness and atrophy beginning in childhood and slowly progressive in the first two decades of life. Neurological examination revealed a symmetrical severe muscle wasting and weakness in distal lower and upper limbs, with claw hands, footdrop with equinovarus deformity and hammer toes, generalized areflexia and normal sensory examination. The electrodiagnostic study revealed a pure chronic motor peripheral nerve involvement without signs of demyelination. The molecular study found the deletion c.561_576del on exon 4 and a deletion of all exon 4, in the SIGMAR1 gene.

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