The diagnosis and management of fragile X syndrome (FXS) have significantly improved in the last three decades, although the current diagnostic techniques are not yet able to precisely identify the number of repeats, methylation status, level of mosaicism, and/or the presence of AGG interruptions. A high number of repeats (>200) in the fragile X messenger ribonucleoprotein 1 gene (FMR1) results in hypermethylation of promoter and gene silencing. The actual molecular diagnosis is performed using a Southern blot, TP-PCR (Triplet-Repeat PCR), MS-PCR (Methylation-Specific PCR), and MS-MLPA (Methylation-Specific MLPA) with some limitations, with multiple assays being necessary to completely characterise a patient with FXS. The actual gold standard diagnosis uses Southern blot; however, it cannot accurately characterise all cases. Optical genome mapping is a new technology that has also been developed to approach the diagnosis of fragile X syndrome. Long-range sequencing represented by PacBio and Oxford Nanopore has the potential to replace the actual diagnosis and offers a complete characterization of molecular profiles in a single test. The new technologies have improved the diagnosis of fragile X syndrome and revealed unknown aberrations, but they are a long way from being used routinely in clinical practice.

The most frequent microdeletion, 22q11.2 deletion syndrome (22q11.2DS), has a wide and variable phenotype that causes difficulties in diagnosis. 22q11.2DS is a contiguous gene syndrome, but due to the existence of several low-copy-number repeat sequences (LCR) it displays a high variety of deletion types: typical deletions LCR A–D—the most common (~90%), proximal deletions LCR A–B, central deletions (LCR B, C–D) and distal deletions (LCR D–E, F). Methods: We conducted a retrospective study of 59 22q11.2SD cases, with the aim of highlighting phenotype–genotype correlations. All cases were tested using MLPA combined kits: SALSA MLPA KIT P245 and P250 (MRC Holland). Results: most cases (76%) presented classic deletion LCR A–D with various severity and phenotypic findings. A total of 14 atypical new deletions were identified: 2 proximal deletions LCR A–B, 1 CES (Cat Eye Syndrome region) to LCR B deletion, 4 nested deletions LCR B–D and 1 LCR C–D, 3 LCR A–E deletions, 1 LCR D–E, and 2 small single gene deletions: delDGCR8 and delTOP3B. Conclusions: This study emphasizes the wide phenotypic variety and incomplete penetrance of 22q11.2DS. Our findings contribute to the genotype–phenotype data regarding different types of 22q11.2 deletions and illustrate the usefulness of MLPA combined kits in 22q11.2DS diagnosis.

Background/Objectives: Ulcerative colitis is a chronic inflammatory bowel disease whose incidence is steadily growing worldwide. The interactions between host genetic susceptibility, gut microbiota and environmental factors determine the onset and relapsing evolution of ulcerative colitis, making it a multifactorial disorder. Methods: A narrative review was conducted to synthesize the available literature on the genes and mechanisms related to ulcerative colitis. Results: The most important independent risk factor is genetics and the candidate genes are associated with inflammation, immune regulation and epithelial permeability. Multiple GWAS have already identified candidate genes and their polymorphisms implicated in ulcerative colitis pathogenesis. Genetic susceptibility is conferred by predisposing variants influencing disease onset and progression, as well as by epigenetic modifications (DNA methylation, microRNAs). Conclusions: This review summarizes the interactions between the functional products encoded by genes linked to ulcerative colitis and immunological factors revealing their common mechanisms.

2q37 microdeletion/deletion syndrome (2q37DS) is one of the most common subtelomeric deletion disorders, caused by a 2q37 deletion of variable size. The syndrome is characterized by a broad and diverse spectrum of clinical findings: characteristic facial dysmorphism, developmental delay/intellectual disability (ID), brachydactyly type E, short stature, obesity, hypotonia in infancy, and abnormal behavior with autism spectrum disorder. Although numerous cases have been described so far, the exact mapping of the genotype and phenotype have not yet been achieved. Materials and Methods: In this study we analyzed nine newly diagnosed cases with 2q37 deletion (3 male/6 female, aged between 2 and 30 years old), and followed up at the Iasi Regional Medical Genetics Centre. All patients were tested first with MLPA using combined kits P036/P070 subtelomeric screening mix and follow-up mix P264; after, the deletion size and location were confirmed via CGH-array. We compared our findings with the data of other cases reported in the literature. Results: From nine cases, four had pure 2q37 deletions of variable sizes, and five presented deletion/duplication rearrangements (with chromosomes 2q, 9q, and 11p). In most cases, characteristic phenotypic aspects were observed: 9/9 facial dysmorphism, 8/9 global developmental delay and ID, 6/9 hypotonia, 5/9 behavior disorders, and 8/9 skeletal anomalies—especially brachydactyly type E. Two cases had obesity, one case had craniosynostosis, and four had heart defects. Other features found in our cases included translucent skin and telangiectasias (6/9), and a hump of fat on the upper thorax (5/9). Conclusions: Our study enriches the literature data by describing new clinical features associated with 2q37 deletion, and possible genotype–phenotype correlations.