Congenital neutropenia, which refers to an inherited deficiency in neutrophils, is a rare pathologic condition that affects approximately 0.0001-0.0009% of the general population. While congenital neutropenia can result from mutations in approximately 30 genes, its leading cause is gain-of-function mutations in the ELANE gene, which encodes the neutrophil granule serine protease, neutrophil elastase. This review focuses on established and novel concepts in the genetic, molecular and cellular mechanisms underlying neutrophil elastase-dependent neutropenia, and discusses possible new avenues for neutropenia research as well as potential novel treatment options that target pathogenic elastase variants.

Kindler Syndrome (KS) is one of the rarest subtypes of epidermolysis bullosa (EB). It is characterised by congenital blistering, skin fragility, photosensitivity, and poikilodermatous skin changes. It is an autosomal recessive condition with an established disease-causing mechanism of having biallelic pathogenic variants in the FERMT1 gene. Multiple variants have been reported worldwide since the discovery in 1954. This case report describes two patients of Chinese descent with molecularly confirmed KS, one diagnosed in infancy while the other in mid-adulthood. It highlights the importance and clinical utility of diagnosing KS in children versus adults. The identification of recurrent c.811C>T variant in both patients also expedited the review of local databases and the existing mutation spectrum KS in East Asians.

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by cystic lung destruction and lymphangiomas and is associated with a high risk of osteoporosis-related bone fractures. Its diagnosis is based on pulmonary anatomo-pathological criteria combined with chest computed tomography. Vascular endothelial growth factor-D is the only serum diagnostic biomarker used in clinical practice, while inhibition of the mammalian target of rapamycin (mTOR) pathway by rapamycin is currently the only reference therapy for LAM. Human cathepsin K (CatK), a potent collagenase predominantly found in osteoclasts, is considered a valuable target for anti-osteoporosis and bone cancer therapy. Recently, CatK, which is overexpressed in lung cysts, was proposed as a putative LAM biomarker. Moreover, CatK may play a role in the LAM pathophysiology by contributing to pulmonary cystic destruction and bone degradation. Accordingly, targeting the collagenolytic activity of CatK by exosite-binding inhibitors, in combination with mTOR inhibition, could represent an innovative therapeutic option for reducing lung destruction in LAM.

Aim: Turner Syndrome (TS) is caused by partial or complete absence of the second sex chromosome in a phenotypic female. TS is associated with recognizable congenital anomalies and chronic health conditions. The principal objective of this study was to evaluate the health-related knowledge and insight of participants.

Methods: In 2015, we founded the UTHealth Turner Syndrome Research Registry for longitudinal follow-up of individuals with TS. Study participants were recruited from UTHealth Houston clinics and the Turner Syndrome Society of the United States. Participants completed a questionnaire about demographics, karyotype, congenital anomalies, health history, frequency of contact with care providers, and knowledge of care providers about TS.

Results: Forty percent of registry participants indicated that they did not know their karyotypes. Knowledge of karyotype, which can predict clinical outcomes in TS, markedly varied by self-reported race and ethnicity but not by age. Participants also reported significant gaps in routine medical and gynecologic care.

Conclusion: We identified knowledge gaps and health disparities that could benefit from improved provider and patient education.

In recent years, accumulating evidence has shown that pulmonary arterial hypertension (PAH) has a strong underlying inflammatory component. Vascular remodeling, a common pathology observed in all forms of pulmonary hypertension (PH), is accompanied by a pronounced accumulation of leukocytes around and within the vessels. Proteolytic products of immune cells, particularly neutrophil and mast cell serine proteases, have been shown to play a central pathogenic role in vascular remodeling and PAH development. Serine proteases are involved in many aspects of the inflammatory response, such as extracellular matrix degradation, regulation of bioavailability of cytokines, chemokines, and growth factors, and dysregulation of their activity can have devastating consequences. In this review, we will focus on immune dysregulation in PAH and shed light on the pro-inflammatory role of serine proteases in vascular pathology observed in the context of this disease.