The CATCH 22 acronym outlines the main clinical features of 22q11.2 deletions (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcemia), usually found in DiGeorge (DGS) and velo-cardio-facial (VCFS) syndromes. Hemizygosity of this region may also be the cause of over 100 different clinical signs. The CATCH 22 locus maps within a 1.5 Mb region, which encompasses several genes. However, no single defect in 22q11.2 hemizygous patients can be ascribed to any gene so far isolated from the critical region of deletion. We have identified a gene in the CATCH 22 critical region, whose functional features and tissue-specific expression suggest a distinct role in embryogenesis. This gene, UFD1L, encodes the human homolog of the yeast ubiquitin fusion degradation 1 protein (UFD1 p), involved in the degradation of ubiquitin fusion proteins. Cloning and characterization of the murine homolog (Ufd1l) showed it to be expressed during embryogenesis in the eyes and in the inner ear primordia. These data suggest that the proteolytic pathway that recognizes ubiquitin fusion proteins for degradation is conserved in vertebrates and that the UFD1L gene hemizygosity is the cause of some of the CATCH 22-associated developmental defects.

Background and Objective: Congenital heart defects (CHD) represent the most frequent human birth defects, occurring in almost 1% of all live newborns. Understanding the effects of gender in the prevalence of CHD has a key role in defining personalized prevention, disease identification, prognosis definition and individualized therapeutic strategies. Recently, the attempt to achieve a holistic approach to patients with CHD cannot be separated from accounting for existing gender differences. The main aim of this narrative review is to provide an overview of gender differences in the epidemiology of CHD. Methods: A standardized research through three electronic databases (PubMed/Scopus/Embase) was performed using a combination of keywords and Medical Subject Headings (MeSH) terms to include congenital heart diseases, gender difference(s), prevalence. Observational, prospective, population based and retrospective studies reporting gender differences in the prevalence of CHD were included. Conference abstracts were excluded as well as studies not written in English language and non-human studies. Further relevant papers were selected by hand-searching of the references list of selected articles. Key Content and Findings: Search results returned 1,904 papers. Screening articles by title and abstracts resulted in 17 articles for full text review. Of these, 10 were included for analysis and additional 11 articles were included after hand searching review of reference lists. A total of 21 articles were included. Conclusions: Our narrative review confirms that there is a significant gender variation in specific CHD subgroups. In particular, we summarized the evidence that there is a significantly greater risk for males to be born with severe CHD and for females with milder CHD subtypes. The etiology of the different distribution of CHD among genders is still under investigation and a deeper understanding of how gender influences the risk for CHD is warranted. In the future, a gender-based management of CHD should become an established medical approach.