RESUMEN
Fucosidosis is a rare lysosomal storage disorder inherited in an autosomal recessive manner. Its estimated frequency is below 1 in 200,000 live births. Its clinical phenotypes include progressive neurological and mental deterioration, coarse facial features, growth retardation, visceromegaly, angiokeratomas, and seizures. The disease is caused by mutations in the FUCA1 gene that lead to deficiency of a-L-fucosidase. Here, we describe the clinical and molecular features of a Thai boy with fucosidosis. Whole exome sequencing and array-based comparative genomic hybridization analysis revealed that the patient was compound heterozygous for a single base-pair deletion (c.670delC; p.P224LfsX2) inherited from his father, and a 3281-base-pair deletion covering exon 3 inherited from his mother. Neither mutation has been reported before so the FUCA1 mutational spectrum is herein expanded.
Asunto(s)
Fucosidosis/genética , Enfermedades por Almacenamiento Lisosomal/genética , alfa-L-Fucosidasa/genética , Adulto , Niño , Hibridación Genómica Comparativa , Exones/genética , Femenino , Fucosidosis/fisiopatología , Genes Recesivos , Humanos , Enfermedades por Almacenamiento Lisosomal/patología , Masculino , Mutación , Linaje , FenotipoRESUMEN
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder caused by mutations in the gene encoding the WAS protein (WASP). Classic WAS is characterized by thrombocytopenia with small-sized platelets, recurrent infections, eczema and increased susceptibility to autoimmune diseases and haematologic malignancies. Here, we reported on seven unrelated Thai individuals with classic WAS. In addition to clinical and immunologic characterization, mutation analysis by PCR-sequencing the entire coding region of WASP was performed. Recurrent and novel mutations were successfully identified. A nonsense mutation, the c.55C>T (p.Q19X), has not been previously described, expanding the mutational spectrum of WASP. The patient with this newly described mutation developed cow's milk allergy manifesting as angioedema and urticaria and had cytomegalovirus infection that was successfully treated with long-term ganciclovir. This study reported long-term follow-up of seven patients with molecular confirmation of WAS and infrequent features in the patient with classic WAS carrying the novel nonsense mutation.