The etiology for the majority of congenital heart defects (CHD) is unknown. We identified a patient with unbalanced atrioventricular septal defect (AVSD) and hypoplastic left ventricle who harbored an ~0.3Mb monoallelic deletion on chromosome 3p14.1. The deletion encompassed the first 4 exons of FOXP1, a gene critical for normal heart development that represses cardiomyocyte proliferation and expression of Nkx2.5. To determine if FOXP1 mutations are found in patients with CHD, we sequenced FOXP1 in 82 patients with AVSD or hypoplastic left heart syndrome. We discovered two patients who harbored a heterozygous c.1702C>T variant in FOXP1 that predicted a potentially deleterious substitution of a highly conserved proline (p.Pro568Ser). This variant was not found in 287 controls but is present in dbSNP at a 0.2% frequency. The orthologous murine Foxp1 p.Pro596Ser mutant protein displayed deficits in luciferase reporter assays and resulted in increased proliferation and Nkx2.5 expression in cardiomyoblasts. Our data suggest that haploinsufficiency of FOXP1 is associated with human CHD.
Langerhans cell histiocytosis (LCH) is an uncommon histiocytic disorder in adults. Clinically, this rare entity can mimic other dermatologic conditions, including hidradenitis suppurativa. A case of LCH is reported with clinical and histologic features of hidradenitis suppurativa, along with a review of these unusual findings. Clinical dermatologists and dermatopathologists benefit from awareness of this unique presentation, which may prompt earlier identification and diagnosis of adult patients with LCH.
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