New mutation in Fabry disease: c.448delG, first phenotypic description

CALABRESE E; BOTTA G; ROZENFELD PA

Molecular Genetics and Metabolism Reports

Elsevier

Año: 2021

2214-4269

Fabry disease (FD) (Anderson-Fabry disease, OMIM 301500) is a genetic disorder caused by a pathogenic variantin the GLA gene on chromosome Xq22 that produces a deficiency in the lysosomal enzyme alpha-galactosidase A.It is transmitted as an X-linked trait, although de novo mutations have been described. The objective of thisreport is to describe the clinical characteristics of a patient with FD who is a carrier of a mutation not previouslystudied, in order to provide information on the genotype-phenotype correlation in this pathology.38-year-old patient who consulted Neurology for positional vertigo. He also reported acroparesthesia,anhidrosis, heat intolerance and episodes of abdominal pain, with postprandial discomfort from 10 years of age.Physical examination showed horizonto-rotatory nystagmus in both looks, the rest of the neurological evaluationdid not present abnormalities. The presence of umbilical and thighs angiokeratomas was identified. Determination of Alpha-Galactosidase in blood was requested: 0.34 μmol/l/h (2.10?10.51 μmol/l/h). Genetic analysisdetected a deletion of a guanine at position 448, in exon 3 of the GLA gene (c.448delG). This mutation wasconsidered to be pathogenic, confirming the diagnosis of FD, although it is not described in the data bases.Genetic counseling and a family pedifree study were performed without finding relatives with this variant of theGLA gene or a family history of FD, which suggests a de novo mutation