RESUMO
BACKGROUND: Esophageal atresia is a major congenital malformation characterized by a complete interruption of the esophageal continuity. It is frequently observed in associations and syndromes. As an isolated finding, it has a multifactorial etiology whose genetic factors are poorly known. Recently, the GST family, especially the GSTM1 null genotype (but not the GSTP1 polymorphism I105V), has been associated with esophageal atresia. These enzymes play a role in phase II detoxification of xenobiotics. Here we present the clinical and molecular findings observed in a patient suggesting that the loss of the GSTP1 allele might predispose to this malformation. CASE: We describe a patient presenting with esophageal atresia associated with developmental delay and facial dysmorphism, whose mother used tobacco and alcohol during the first 2 months of her pregnancy. Microdeletion/microduplication analysis was performed using comparative genomic hybridization and a 180K Agilent array. It detected a de novo 2 Mb chromosome 11q13.1.q13.2 deletion. CONCLUSION: The deleted chromosomal segment includes the GSTP1 gene. We hypothesize that the deletion of one GSTP1 allele (an isoform highly expressed in embryonic tissues), associated with specific environmental factors, such as tobacco and alcohol, could cause the esophageal atresia observed in our patient.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 11/genética , Deficiências do Desenvolvimento/genética , Atresia Esofágica/genética , Glutationa S-Transferase pi , Atrofia Muscular/genética , Anormalidades Múltiplas/enzimologia , Anormalidades Múltiplas/patologia , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Alelos , Anormalidades Craniofaciais , Deficiências do Desenvolvimento/enzimologia , Deficiências do Desenvolvimento/patologia , Atresia Esofágica/enzimologia , Atresia Esofágica/patologia , Fácies , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Atrofia Muscular/enzimologia , Atrofia Muscular/patologia , Gravidez , Fumar/efeitos adversosRESUMO
Purine nucleoside phosphorylase deficiency is a primary immunodeficiency syndrome characterized by the triad of recurrent infection, neurologic dysfunction, and autoimmunity. This patient presented atypically with few infections and normal T-cell function. Progressive lymphopenia, ataxia, and developmental delay led to diagnosis. Umbilical cord blood transplantation corrected the immunodeficiency.