RESUMO
OBJECTIVE: To identify the underlying genetic cause for recurrent intrauterine fetal death (IUFD) of males. METHODS: Whole genome sequencing was performed on DNA from five healthy obligatory carrier females and an unaffected male offspring of a multigenerational pedigree with recurrent second-trimester IUFD of males (n = 19). When documented, all deaths occurred at ≤20 weeks of gestation. Hydrops fetalis was diagnosed at death in the most recent case. RESULTS: Following variant filtering based on a recessive X-linked inheritance pattern, a rare FOXP3 frameshift mutation (p.D303fs*87) that results in a premature truncation of the protein was discovered. Sanger sequencing confirmed the mutation in the affected fetus. The FOXP3 gene encodes for a transcriptional regulator critical to the function of regulatory T cells. FOXP3 mutations are associated with immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome which exclusively affects males and may present with a potentially life-threatening complex autoimmune disorder in early childhood. CONCLUSIONS: Here, we demonstrate the utility of whole genome sequencing-based pedigree analysis to identify the genetic cause for recurrent IUFD when chromosome studies, including microarray analysis, are normal. Further studies are needed to determine the prevalence of FOXP3-mediated IUFD in males. © 2017 John Wiley & Sons, Ltd.
Assuntos
Morte Fetal/etiologia , Sequenciamento Completo do Genoma , DNA/análise , Diabetes Mellitus Tipo 1/congênito , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Diarreia/genética , Diarreia/patologia , Feminino , Fatores de Transcrição Forkhead/genética , Mutação da Fase de Leitura/genética , Genes Ligados ao Cromossomo X , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Idade Gestacional , Humanos , Hidropisia Fetal/genética , Doenças do Sistema Imunitário/congênito , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/patologia , Masculino , Linhagem , Gravidez , Segundo Trimestre da GravidezRESUMO
The spiritual needs of couples (9 mothers and 5 fathers) who were planning to terminate wanted second trimester pregnancies because of serious fetal anomalies were surveyed. Their greatest needs were for a "guidance from a higher power" and for "someone to pray for them." Unlike other reported groups of patients, they did not want or expect their healthcare team to discuss their faith, or to pray with them. Most would prefer support from their own pastors, but their religious community was involved to only a small extent. They would welcome support from hospital chaplains, who could play a substantive and unique pastoral role in this clinical context.
