RESUMEN
Donnai-Barrow syndrome (DBS) is an autosomal recessive disorder characterized by typical craniofacial features, vision and hearing loss, intellectual disability, agenesis of the corpus callosum (ACC), congenital diaphragmatic hernia (CDH), and omphalocele. This condition is associated with loss-of-function mutations in the LRP2 gene. Few cases have been described in the literature. In our case, CDH and ACC were prenatally diagnosed by ultrasound, and the fetus was the product of a first-degree union. Single-nucleotide polymorphism-microarray showed large regions of homozygosity. Whole exome sequencing (WES) was performed and revealed a homozygous frameshift pathogenic variant in LRP2 (c.6978dupG). Here, we present a case of DBS, which diagnosed prenatally via WES in a fetus with CDH and ACC.
Asunto(s)
Anomalías Múltiples/genética , Agenesia del Cuerpo Calloso/genética , Pérdida Auditiva Sensorineural/genética , Hernias Diafragmáticas Congénitas/genética , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Miopía/genética , Proteinuria/genética , Defectos Congénitos del Transporte Tubular Renal/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/patología , Adulto , Agenesia del Cuerpo Calloso/diagnóstico , Agenesia del Cuerpo Calloso/diagnóstico por imagen , Agenesia del Cuerpo Calloso/patología , Agenesia del Cuerpo Calloso/terapia , Consanguinidad , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/diagnóstico por imagen , Pérdida Auditiva Sensorineural/patología , Hernias Diafragmáticas Congénitas/diagnóstico , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/patología , Homocigoto , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Discapacidad Intelectual/terapia , Mutación con Pérdida de Función/genética , Miopía/diagnóstico , Miopía/diagnóstico por imagen , Miopía/patología , Diagnóstico Prenatal/métodos , Proteinuria/diagnóstico , Proteinuria/diagnóstico por imagen , Proteinuria/patología , Defectos Congénitos del Transporte Tubular Renal/diagnóstico , Defectos Congénitos del Transporte Tubular Renal/diagnóstico por imagen , Defectos Congénitos del Transporte Tubular Renal/patología , Ultrasonografía , Secuenciación del Exoma/métodosRESUMEN
BACKGROUND: Delayed discussion about infertility with individuals affected by Turner syndrome (TS) has been found to result in psychological and social harm. The aim of this study was to identify barriers experienced when discussing infertility and determine resource types that may facilitate this conversation. METHODS: An electronic survey, given to caregivers of girls with TS diagnosed at <5 years. RESULTS AND CONCLUSIONS: Fifty percent of parents surveyed had spoken to their daughter about their possible infertility. Parents who had not yet discussed infertility with their daughter had younger daughters and reported more barriers in having the conversation. Although most individuals did not use resources to facilitate the conversation, they did express interest in additional resources.
Asunto(s)
Barreras de Comunicación , Infertilidad Femenina/fisiopatología , Síndrome de Turner/fisiopatología , Femenino , HumanosRESUMEN
BACKGROUND: The A/WySn mouse strain with 15 to 20% penetrance of cleft lip and palate (CLP) is an animal model for human multifactorial CLP. The CLP is due to two unlinked genes that interact epistatically, Wnt9b(clf1) and clf2, plus a maternal effect. The Wnt9b(clf1) mutation is an IAP transposon insertion. The clf2 gene, with unknown function, was located in a 13.6 Mb region of chromosome 13 containing 145 genes. METHODS: To reduce the clf2 candidate region, 1146 mice segregating for A/WySn and C57BL/6J alleles at clf2 were screened for recombinants by simple sequence-length polymorphism haplotypes; recombinants' testcross progeny were typed for CLP and simple-sequence length polymorphisms. To identify the function of clf2, the effect of clf2 genotype on risk of CLP was tested in Wnt9b(null/null) knockouts and in compound mutants (Wnt9b(clf1/null) ), and the methylation of the IAP at Wnt9b was assayed in the Wnt9b(clf1/null) mutants by combined bisulfite restriction analysis. RESULTS: The location of clf2 was redefined to 3.0 Mb between Cntnap3 and AK029746 containing 48 genes, of which 30 are Zfp genes. The clf2 genotype had no detectable effect on Wnt9b(null/null) embryos, but strongly affected risk of CLP and methylation of the IAP in Wnt9b(clf1/null) embryos. CLP was associated with low levels of methylation of the IAP. CONCLUSIONS: The clf2 gene is the first identified polymorphism that affects the epigenetic methylation and silencing of IAP retrotransposons. This CLP model raises the question of whether parallel epigenetic factors are involved in risk and environmental sensitivity of human CLP.