Kristi S. Borowski

Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations

We identified four girls with a consistent constellation of facial dysmorphism and malformations previously reported in a single mother–daughter pair. Toe syndactyly, telecanthus and anogenital and renal malformations were present in all affected individuals; thus, we propose the name STAR syndrome for this disorder. Using array CGH, qPCR and sequence analysis, we found causative mutations in FAM58A on Xq28 in all affected individuals, suggesting an X-linked dominant inheritance pattern for this recognizable syndrome.

A proposed method to predict preterm birth using clinical data, standard maternal serum screening, and cholesterol

OBJECTIVEnThe objective of the study was to create a predictive model for preterm birth (PTB) from available clinical data and serum analytes.nnnSTUDY DESIGNnSerum analytes and routine pregnancy screening plus cholesterol and corresponding health information were linked to birth certificate data for a cohort of 2699 Iowa women with serum sampled in the first and second trimester. Stepwise logistic regression was used to select the best predictive model for PTB.nnnRESULTSnSerum screening markers remained significant predictors of PTB, even after controlling for maternal characteristics. The best predictive model included maternal characteristics, first-trimester total cholesterol, total cholesterol change between trimesters, and second-trimester alpha-fetoprotein and inhibin A. The model showed better discriminatory ability than PTB history alone and performed similarly in subgroups of women without past PTB.nnnCONCLUSIONnUsing clinical and serum screening data, a potentially useful predictor of PTB was constructed. Validation and replication in other populations, and incorporation of other measures that identify PTB risk, like cervical length, can be a step toward identifying additional women who may benefit from new or currently available interventions.

Variations in CRHR1 are associated with persistent pulmonary hypertension of the newborn

Introduction:Persistent pulmonary hypertension of the newborn (PPHN) is associated with substantial infant morbidity and mortality. Recently, genetic associations have been found in idiopathic pulmonary arterial hypertension.Results:PPHN was significantly (P < 0.05) associated with genetic variants in corticotropin-releasing hormone (CRH) receptor 1, CRHR1 and CRH-binding protein, CRHBP. Association with CRHR1 rs4458044 passed the Bonferroni threshold for significance. No mutations were found in the bone morphogenetic protein receptor type II (BMPR2) gene.Discussion:We describe previously unreported genetic associations between PPHN and CRHR1 and CRHBP. These findings may have implications for further understanding the pathophysiology of PPHN and treatment.Methods:We performed a family-based candidate gene study to examine a genetic association with PPHN and sequenced the BMPR2 gene in 72 individuals. We enrolled 110 families with infants diagnosed with PPHN based on inclusion criteria. After medical chart review, 22 subjects were excluded based on predefined criteria, and DNA samples from 88 affected infants and at least one parent per infant were collected and genotyped. Thirty-two single-nucleotide polymorphisms in 12 genes involved in vasoconstriction/vasodilation, lung development, surfactant regulation, or vascular endothelial cell function were investigated using family-based association tests.

Combined elevated midpregnancy tumor necrosis factor alpha and hyperlipidemia in pregnancies resulting in early preterm birth

OBJECTIVEnThe objective of the study was to determine whether pregnancies resulting in early preterm birth (PTB) (<30 weeks) were more likely than term pregnancies to have elevated midtrimester serum tumor necrosis factor alpha (TNF-α) levels combined with lipid patterns suggestive of hyperlipidemia.nnnSTUDY DESIGNnIn 2 nested case-control samples drawn from California and Iowa cohorts, we examined the frequency of elevated midpregnancy serum TNF-α levels (in the fourth quartile [4Q]) and lipid patterns suggestive of hyperlipidemia (eg, total cholesterol, low-density-lipoproteins, or triglycerides in the 4Q, high-density lipoproteins in the first quartile) (considered independently and by co-occurrence) in pregnancies resulting in early PTB compared with those resulting in term birth (n = 108 in California and n = 734 in Iowa). Odds ratios (ORs) and 95% confidence intervals (CIs) estimated in logistic regression models were used for comparisons.nnnRESULTSnEarly preterm pregnancies were 2-4 times more likely than term pregnancies to have a TNF-α level in the 4Q co-occurring with indicators of hyperlipidemia (37.5% vs 13.9% in the California sample (adjusted OR, 4.0; 95% CI, 1.1-16.3) and 26.3% vs 14.9% in the Iowa sample (adjusted OR, 2.7; 95% CI, 1.1-6.3). No differences between early preterm and term pregnancies were observed when TNF-α or target lipid abnormalities occurred in isolation. Observed differences were not explicable to any maternal or infant characteristics.nnnCONCLUSIONnPregnancies resulting in early PTB were more likely than term pregnancies to have elevated midpregnancy TNF-α levels in combination with lipid patterns suggestive of hyperlipidemia.