Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the GLA Gene Associated with the Classical Phenotype of Fabry Disease.
We report on the clinical, biochemical, and genetic findings of a large family with the classical phenotype of Fabry disease due to the novel nonsense mutation c.607G>T (p.E203X) of the GLA gene, which occurs in the active site of the α-galactosidase A enzyme. This report highlights that (i) Fabry disease diagnosis should be considered in all cases of unexplained left ventricular hypertrophy (LVH), even in its milder forms; (ii) a complete evaluation of patients with unexplained LVH is important to find diagnostic red flags of treatable causes of LVH, such as Fabry disease; (iii) cascade family screening is paramount to the earlier diagnosis and treatment of other affected family members; and (iv) the Fabry disease phenotype is highly variable in heterozygote females, even within the same family.
Department of Cardiology, Reference Center on Lysosomal Storage Disorders, Hospital Senhora da Oliveira, Guimarães, Portugal.
Olga
O
Azevedo
Miguel
M
Gago
Gabriel
G
Miltenberger-Miltenyi
Paulo
P
Gaspar
Nuno
N
Sousa
Damião
D
Cunha
D000328:Adult; D018389:Codon, Nonsense; D004452:Echocardiography; D000795:Fabry Disease / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012737:Sex Factors; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics*
D018389:Codon, Nonsense; C576330:GLA protein, human; D000519:alpha-Galactosidase
Classical phenotype; Fabry disease; GLA gene; Left ventricular hypertrophy; Mutation; Nonsense