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Recurrent microdeletions of 8p23.1 that include GATA4 and SOX7 confer a high risk of both congenital diaphragmatic hernia (CDH) and cardiac defects. Although GATA4-deficient mice have both CDH and cardiac defects, no humans with cardiac defects attributed to GATA4 mutations have been reported to have CDH. We were also unable to identify deleterious GATA4(More)
R ett syndrome (RTT; MIM 312750) is a neurodevelopmental disorder with an onset in early childhood that affects 1/10 000–1/15 000 females. After a period of relatively normal development, girls with RTT present with developmental arrest, usually by 12–18 months of age, followed by rapid deterioration with regression of speech and purposeful hand movements.(More)
Congenital diaphragmatic hernia (CDH) is a common life-threatening birth defect. Recessive mutations in the FRAS1-related extracellular matrix 1 (FREM1) gene have been shown to cause bifid nose with or without anorectal and renal anomalies (BNAR) syndrome and Manitoba oculotrichoanal (MOTA) syndrome, but have not been previously implicated in the(More)
Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and found heterozygous and mosaic mutations in PORCN in other(More)
The FRAS1-related extracellular matrix 1 (FREM1) gene encodes an extracellular matrix protein that plays a critical role in the development of multiple organ systems. In humans, recessive mutations in FREM1 cause eye defects, congenital diaphragmatic hernia, renal anomalies and anorectal malformations including anteriorly placed anus. A similar(More)
BACKGROUND Congenital diaphragmatic hernia (CDH) is a life threatening birth defect. Most of the genetic factors that contribute to the development of CDH remain unidentified. OBJECTIVE To identify genomic alterations that contribute to the development of diaphragmatic defects. METHODS A cohort of 45 unrelated patients with CDH or diaphragmatic(More)
Individuals with terminal and interstitial deletions of chromosome 1p36 have a spectrum of defects that includes eye anomalies, postnatal growth deficiency, structural brain anomalies, seizures, cognitive impairment, delayed motor development, behavior problems, hearing loss, cardiovascular malformations, cardiomyopathy, and renal anomalies. The proximal(More)
The pyridine ring is a potent pharmacophore in alkaloid natural products. Nonetheless, its biosynthetic pathways are poorly understood. Rubrolones A and B are tropolone alkaloid natural products possessing a unique tetra-substituted pyridine moiety. Here, we report the gene cluster and propose a biosynthetic pathway for rubrolones, identifying a key(More)
R ett syndrome (RTT; MIM 312750) is a neurodevelop-mental disorder with an onset in early childhood that affects 1/10 000–1/15 000 females. After a period of relatively normal development, girls with RTT present with developmental arrest, usually by 12–18 months of age, followed by rapid deterioration with regression of speech and purposeful hand movements.(More)
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