👤 Silvia Cadamuro

Cholestatic liver diseases are a heterogeneous group of conditions that can remain unexplained despite a comprehensive diagnostic assessment. Genetic disorders may underlie many of these unexplained adult-onset cholestasis cases. However, genetic testing in adults has been focused on genes linked to progressive familial intrahepatic cholestasis (PFIC). This study evaluated the diagnostic utility of whole exome sequencing (WES) by targeting a broader set of genes beyond PFIC genes. Adults with unexplained cholestatic liver disease from one tertiary center underwent WES. Pathogenic and rare damaging variants in candidate cholestatic and liver disease genes were prioritized, and genotype-phenotype correlations were conducted. Twenty-one patients with three distinct cholestatic phenotypes (recurrent lithiasis, intrahepatic cholestasis, and primary sclerosing cholangitis with unusual features) were included. WES yielded a genetic diagnosis of inherited cholestatic or liver disorder mimicking the cholestatic phenotype in 5 cases (23.8%). ABCB4 was the causative gene in 2 cases (40.0%), whereas genes outside the PFIC spectrum (ABCC2, PPOX, APOB) accounted for the other 3 (60.0%). This study highlights the value of WES in the diagnostic workup of adult-onset cholestatic liver disease and expands our understanding of its genetic landscape, paving the way for larger-scale studies. Show less

To evaluate a pathological condition on a skeleton from medieval Veneto (Italy). A male skeleton (T97), aged 35-50 years, from the Early Medieval phase of an archaeological site in the Venetian Lagoon, was examined and radiocarbon dated to Cal 954-1052 CE. The skeletal remains were examined by anthropological methods, by radiographic imaging, full skeletal CT scans, and histological examination. A differential diagnosis was conducted following established protocols. A total of 129 osteochondromas were observed. Both types were evident: sessile and pedunculated. Osteochondromas were evident in most bones of the appendicular skeleton; the skull, vertebrae and ribs remained unaffected. Short stature and forearm deformity were also observed. The differential diagnosis identifies these pathological findings as manifestations of an advanced form of multiple osteochondromas (MO). The significance of this diagnosis lies in its ability to shed light on the natural progression of MO, particularly in the absence of modern surgical interventions. Additionally, it highlights the survival and adaptation of an individual with disabilities within a medieval society. To achieve a definitive confirmation of this diagnosis, genetic testing would be essential. The discovery of only one individual with this condition among 181 analyzed in the context prevents further broader conclusions. Genetic Analysis to confirm the diagnosis of MO and investigate potential genetic mutations, such as those in the EXT1 and EXT2 genes. Show less