Partial penetrance and phenotypic variability of aplasia of lacrimal and salivary glands caused by a novel FGF10 donor splice-site mutation.

Thirteen affected individuals of six generations of a single kindred presented with epiphora evident from infancy. Physical exam and Schirmer test revealed variable expression of tear deficiency, congenital punctal atresia, and dry mouth with multiple caries, without concomitant abnormalities of the ears or digits, commensurate with a diagnosis of aplasia of the lacrimal and salivary glands (ALSG). Reconstruction of the upper lacrimal drainage system was performed in some of the affected individuals. Genetic analysis, testing six affected individuals and three non-affected family members, identified a single novel heterozygous splice-site variant, c.429 + 1, G > T in fibroblast growth factor 10 (FGF10) (NM_004465.1), segregating throughout the family as expected for dominant heredity. RT-PCR assays of HEK-293 cells transfected with wild type or mutant FGF10 demonstrated that the variant causes skipping of Exon 2. Notably, individuals sharing the same variant exhibited phenotypic variability, with unilateral or bilateral epiphora, as well as variable expression of dry mouth and caries. Moreover, one of the variant carriers had no ALSG-related clinical findings, demonstrating incomplete penetrance. While coding mutations in FGF10 are known to cause malformations in the nasolacrimal system, this is the second FGF10 splice-site variant and the first donor-site variant reported to cause ALSG. Thus, our study of a unique large kindred with multiple affected individuals heterozygous for the same FGF10 variant highlights intronic splice-site mutations and phenotypic variability/partial penetrance in ALSG.

Correlation between baseline immature platelets fraction levels and peak troponin in patients with acute myocardial infarction.

INTRODUCTION: Elevated peak cardiac troponin levels have been linked with increased morbidity and mortality in patients with acute myocardial infarction (AMI). Immature Platelets are young and relatively large platelets that are hyper-reactive and pro-thrombotic compared to regular platelets. Increased immature platelet fraction (IPF) has been associated with an elevated risk of thrombotic events. We hypothesize that patients with higher IPF levels during AMI, will experience a more severe infarct, leading to elevated peak troponin levels. METHODS: Clinical data from patients admitted to the cardiology division between 2018 and 2022, who were diagnosed with AMI and underwent an IPF testing. Univariate and multivariate regression analyses were performed to identify predictors of elevated peak troponin. RESULTS: Among the 277 patients diagnosed with AMI who underwent IPF testing, 113 had (STEMI) and 164 had (NSTEMI). The median value of IPF of 4.2% was used as the threshold for defining elevated IPF. Notably, among STEMI patients, those with IPF ≥ 4.2% had significantly higher peak troponin levels ( P  = 0.021). Conversely, no significant difference in peak troponin levels was observed among NSTEMI patients ( P  = 0.348). Multivariate analysis identified patients with STEMI in the higher IPF group as one of the significant predictors for elevated peak troponin levels. CONCLUSION: This study revealed a correlation between higher baseline IPF levels and increased peak troponin levels specifically in STEMI patients, while no such association was found in NSTEMI patients. Incorporating IPF levels above the median into risk stratification scores for STEMI patients may provide valuable support for adopting a more proactive therapeutic approach.