Jacobsen syndrome is a MCA/MR contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. To date, over 200 cases have been reported. The prevalence has been estimated at 1/100,000 births, with a female/male ratio 2:1. The most common clinical features include pre- and postnatal physical growth retardation, psychomotor retardation, and characteristic facial dysmorphism (skull deformities, hypertelorism, ptosis, coloboma, downslanting palpebral fissures, epicanthal folds, broad nasal bridge, short nose, v-shaped mouth, small ears, low set posteriorly rotated ears). Abnormal platelet function, thrombocytopenia or pancytopenia are usually present at birth. Patients commonly have malformations of the heart, kidney, gastrointestinal tract, genitalia, central nervous system and skeleton. Ocular, hearing, immunological and hormonal problems may be also present. The deletion size ranges from ~7 to 20 Mb, with the proximal breakpoint within or telomeric to subband 11q23.3 and the deletion extending usually to the telomere. The deletion is de novo in 85% of reported cases, and in 15% of cases it results from an unbalanced segregation of a familial balanced translocation or from other chromosome rearrangements. In a minority of cases the breakpoint is at the FRA11B fragile site. Diagnosis is based on clinical findings (intellectual deficit, facial dysmorphic features and thrombocytopenia) and confirmed by cytogenetics analysis. Differential diagnoses include Turner and Noonan syndromes, and acquired thrombocytopenia due to sepsis. Prenatal diagnosis of 11q deletion is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis. Management is multi-disciplinary and requires evaluation by general pediatrician, pediatric cardiologist, neurologist, ophthalmologist. Auditory tests, blood tests, endocrine and immunological assessment and follow-up should be offered to all patients. Cardiac malformations can be very severe and require heart surgery in the neonatal period. Newborns with Jacobsen syndrome may have difficulties in feeding and tube feeding may be necessary. Special attention should be devoted due to hematological problems. About 20% of children die during the first two years of life, most commonly related to complications from congenital heart disease, and less commonly from bleeding. For patients who survive the neonatal period and infancy, the life expectancy remains unknown.

Background/Objectives: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of the CAG nucleotide repeat in the first exon of the huntingtin (HTT) gene. The disease typically manifests between the second and third decades of life and progresses gradually. The pathogenesis of HD involves the dysregulation of gene expression, influenced by various molecular processes ranging from transcription to protein stability. Methods: To investigate potential variations in gene expression associated with HD, a transcriptome study was conducted using peripheral blood mononuclear cell samples from 15 HD patients and 15 controls, all of Sicilian origin. Results: The analysis identified 7179 statistically significant differentially expressed genes between the two groups. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were applied to identify the pathways affected by these differentially expressed mRNAs. The GSEA results highlighted significant associations between HD and GO pathways related to ribosomal functions and structure. These pathways were predominantly characterized by negative expression, with a substantial number of genes showing dysregulation. This suggests that the molecular processes leading to protein translation via ribosomes may be impaired in HD. Furthermore, dysregulation was observed in genes and non-coding RNAs involved in regulatory roles across various transcriptional processes. Conclusions: These findings support the hypothesis that the entire process, from transcription to translation, is disrupted in HD patients carrying the CAG repeat expansion in the first exon of the HTT gene.

Background/Objectives: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG nucleotide repeat expansion in the Huntingtin (HTT) gene. Dysregulation of microRNAs (miRNAs), key post-transcriptional regulators of gene expression, has been implicated in HD pathogenesis, although their specific roles remain incompletely understood. Methods: Peripheral blood mononuclear cells from Sicilian HD patients and matched healthy controls were subjected to small RNA sequencing. Differential expression analysis was conducted using DESeq2 (version 1.44.0), with significance defined as |fold change| ≥ 1.5 and adjusted p ≤ 0.05. Ingenuity Pathway Analysis (IPA) was applied to assess functional enrichment, focusing on neurological diseases, inflammatory processes, and miRNA–RNA messenger (mRNA) interaction networks. Results: A total of 790 differentially expressed miRNAs were identified in HD patients (270 upregulated and 520 downregulated). IPA revealed enrichment in pathways related to organismal injury, neurological disease, and inflammatory responses. Four major regulatory networks linked differentially expressed miRNAs to neurodegenerative processes, with target genes involved in neuroinflammation, cellular stress responses, and metabolic dysfunction. Cross-referencing with previous RNA-seq data identified 5721 high-confidence miRNA–mRNA interactions, implicating 721 target genes across 54 key canonical pathways. Conclusions: HD patients exhibit a distinct and reproducible peripheral blood miRNA expression signature. These dysregulated miRNAs may represent accessible biomarkers and provide mechanistic insights into HD pathogenesis, with potential applications for diagnosis, prognosis, and therapeutic development.

Objectives: Sickle Cell Disease (SCD) has a significant impact on the musculoskeletal system. The use of the Oxford Hip (OHS) and Shoulder score (OSS) as patient-reported outcome measures (PROMs) revealed a high rate of long-term impairment in joints with a pre-existing diagnosis of avascular necrosis (AVN). With this study, we aimed at detecting dysfunction in joints apparently not affected by AVN. Methods: This is a subgroup analysis of a previous core study assessing the OHS and OSS in 47 SCD patients with a pre-existing diagnosis of AVN. For this study, only patients with a pre-existing diagnosis of isolated AVN (only hip or only shoulder) were selected, and the OHS or OSS was measured in previously unaffected joints. Results: Among 37 patients with isolated AVN, 19 (51%) patients presented abnormal scores in the apparently unaffected joint; 16 (50%) patients with pre-existing isolated hip AVN had an abnormal OSS; and 9 (56%) had moderate to severe shoulder impairment. All patients with pre-existing isolated shoulder AVN had an abnormal OHS, with severe hip impairment in two out of three. As per clinical practice, patients with an abnormal score were prescribed joint magnetic resonance imaging (MRI) and/or X-rays. Only 10 out 19 (53%) performed imaging studies and all showed signs of AVN. Conclusions: Abnormal OHS and OSS values indicated a high rate of joint dysfunction in sites apparently not affected by AVN. The routine use of these PROMs should be applied to all SCD adults and subjects with a pathological score should have priority access to diagnostic radiological tests.