Hearing loss is the most frequent sensorineural disorder, affecting approximately 1:1000 newborns. Hereditary forms (HHL) represent 50–60% of cases, highlighting the relevance of genetic testing in deaf patients. HHL is classified as non-syndromic (NSHL—70% of cases) or syndromic (SHL—30% of cases). In this study, a multistep and integrative approach aimed at identifying the molecular cause of HHL in 102 patients, whose GJB2 analysis already showed a negative result, is described. In NSHL patients, multiplex ligation probe amplification and long-range PCR analyses of the STRC gene solved 13 cases, while whole exome sequencing (WES) identified the genetic diagnosis in 26 additional ones, with a total detection rate of 47.6%. Concerning SHL, WES detected the molecular cause in 55% of cases. Peculiar findings are represented by the identification of four subjects displaying a dual molecular diagnosis and eight affected by non-syndromic mimics, five of them presenting Usher syndrome type 2. Overall, this study provides a detailed characterisation of the genetic causes of HHL in the Italian population. Furthermore, we highlighted the frequency of Usher syndrome type 2 carriers in the Italian population to pave the way for a more effective implementation of diagnostic and follow-up strategies for this disease.

Highlights d PIN1 stabilizes HP1a in complex with LaminB in a phosphorylation-dependent manner d PIN1 function maintains nuclear envelope structure under mechanical stress d PIN1 loss causes HP1a degradation, heterochromatin relaxation, transposon derepression d Loss of PIN1 nucleo-protective function contributes to Alzheimer's disease

Malocclusions and temporomandibular disorders (TMDs) are oral health problems that are spread worldwide. To date, few studies focused on their prevalence and associated risk factors are available. This study aims to define the prevalence and distribution of odontostomatological traits and evaluate specific risk factors in isolated villages in north-eastern Italy, taking advantage of their environmental homogeneity. Nine hundred and forty-four participants aged six to eighty-nine years were enrolled. Thirty-one odontostomatological phenotypes, classified into five domains (airways, bad habits, extraoral and intraoral parameters, TMDs, and teeth), were evaluated. A descriptive statistical analysis was performed; mixed logistic models were used to test the relationships among the traits. According to the study’s findings, Angle’s class I was prevalent (65.3%) followed by class II malocclusion (24.3%); class III and reversed overjet were the least frequent malocclusions (10.4% and 1.8%, respectively). Temporomandibular joint (TMJ) click/noise was prevalent among TMDs (34.7%). The statistically significant (p-value < 0.05) risk factors were ankyloglossia for phonetic issues (OR 1.90) and bruxism for TMJ click/noise (OR 1.70) and pain (OR 2.20). Overall, this work provides a picture of the prevalence of malocclusions and TMDs in a large Italian sample and reveals risk factors to take into account in the development of preventive strategies and treatments.

Eating behavior (EB) is a complex system influenced by many factors, but an undisputed role is played by the senses. In this work, we examined the effect of the sensory capacities on EB in 1152 Italian adult individuals. After administering a questionnaire on EB and assessing sensory performance through standard audiometric, olfactory, and taste tests, the prevalence of reduced sensory capacities (RSCs) and the correlation with selected risk factors were calculated. Regression models, structural equation modelling, and conditional recursive partitioning were used to investigate the relationship between variables. Around 70% of the subjects show reduced capacities in at least one sense, with taste being the most prevalent (55.21%). Male sex, aging, and low educational level are risk factors for RSCs. The increased number of senses with reduced capacities is a predictor of diminished food adventurousness and lower liking for vegetables, fish, and alcoholic beverages, while reduced capacities (RCs) in taste is a predictor of lower liking for alcoholic beverages and sweets. Overall, in addition to providing an overall picture of RSCs in Italian samples, our study reveals the association of RSCs with EB variables. This finding could have a relevant role in influencing individuals’ dietary habits and, therefore, health status.

Endometriosis (EM) is a common multifactorial gynaecological disorder. Although Genome-Wide Association Studies have largely been employed, the current knowledge of the genetic mechanisms underlying EM is far from complete, and other approaches are needed. To this purpose, whole-exome sequencing (WES) was performed on a deeply characterised cohort of 80 EM patients aimed at the identification of rare and damaging variants within 46 EM-associated genes and novel candidates. WES analysis detected 63 rare, predicted, and damaging heterozygous variants within 24 genes in 63% of the EM patients. In particular, (1) a total of 43% of patients carried variants within 13 recurrent genes (FCRL3, LAMA5, SYNE1, SYNE2, GREB1, MAP3K4, C3, MMP3, MMP9, TYK2, VEGFA, VEZT, RHOJ); (2) a total of 8.8% carried private variants within eight genes (KAZN, IL18, WT1, CYP19A1, IL1A, IL2RB, LILRB2, ZNF366); (3) a total of 24% carried variants within three novel candidates (ABCA13, NEB, CSMD1). Finally, to deepen the polygenic architecture of EM, a comprehensive evaluation of the analysed genes was performed, revealing a higher burden (p < 0.05) of genes harbouring rare and damaging variants in the EM patients than in the controls. These results highlight new insights into EM genetics, allowing for the definition of novel genotype–phenotype correlations, thereby contributing, in a long-term perspective, to the development of personalised care for EM patients.