Seasonal pattern of the diagnosis of cutaneous melanoma: a hospital-based study in a Mediterranean country

Background Several investigators have described a seasonal variation in the diagnosis of cutaneous melanoma. Limited data exist on the seasonality of melanoma diagnosis in Southern European countries. Patients and methods The seasonal pattern of diagnosis was analyzed in 404 Greek patients diagnosed with cutaneous melanoma (CM) between 1996 and 2004. A summer-to-winter ratio was determined overall and in relation to gender, age, anatomic site, histopathologic type, and tumor thickness. Results The summer-to-winter ratio was 1.53 for all patients ( 95% Cl [confidence interval]: 1.15-2.02) with a ratio of 1.83 for women (95% Cl: 1.20-2.78) and 1.28 for men ( 95% Cl: 0.87-1.88). A seasonal pattern of melanoma diagnosis was observed for patients younger than 50 years of age (1.70, 95% Cl: 1.05-2.74) and between 50 and 69 years ( 1.64, 95% Cl: 1.05-2.56), for melanoma located on the upper or lower extremities (2.50, 95% Cl: 1.12-5.56 and 2.23, 95% Cl: 1.19-4.18, respectively), for superficial spreading and nodular melanomas (1.73, 95% Cl: 1.12-2.69 and 1.52 95% Cl: 0.96-2.41) and for melanomas with a tumor thickness of 1-2 mm (1.69, 95% Cl: 0.91-3.12) and > 4 mm (2.13, 95% Cl: 1.04-4.35). Conclusions No major differences were seen in the seasonal distribution of CM diagnosis in a Mediterranean population compared to previously reported results. A better ascertainment of the skin during the summer and an increased awareness due to the melanoma screening campaigns are the more likely reasons for the seasonality of melanoma diagnosis in Greece

CDKN2A/CDK4 Status in Greek Patients with Familial Melanoma and Association with Clinico-epidemiological Parameters

Approximately 5–10% of melanoma cases occur in a familial context. CDKN2A/CDK4 were the first high-penetrance melanoma genes identified. The aims of this study were to evaluate CDKN2A/CDK4 variants in Greek familial melanoma patients and to correlate the mutational status with specific clinico-epidemiological characteristics. A cross-sectional study was conducted by genotyping CDKN2A/CDK4 variants and selected MC1R polymorphisms in 52 melanoma-prone families. Descriptive statistics were calculated and comparisons were made using the χ2 test, Fisher’s exact test and Student’s t-test for statistical analysis, as appropriate. CDKN2A variants were detected in 46.2% of melanoma-prone families, while a CDK4 variant was found in only one family. This study confirmed that, in the Greek population, the age at melanoma diagnosis was lower in patients carrying a variant in CDKN2A compared with wild-type patients. No statistically significant associations were found between CDKN2A mutational status and MC1R polymorphisms

Novel and Founder Pathogenic Variants in X-Linked Alport Syndrome Families in Greece

Alport syndrome (AS) is the most frequent monogenic inherited glomerulopathy and is also genetically and clinically heterogeneous. It is caused by semi-dominant pathogenic variants in the X-linked COL4A5 (NM_000495.5) gene or recessive variants in the COL4A3/COL4A4 (NM_000091.4/NM_000092.4) genes. The disease manifests in early childhood with persistent microhematuria and can progress to proteinuria and kidney failure in adolescence or early adulthood if left untreated. On biopsy, pathognomonic features include alternate thinning, thickening and lamellation of the glomerular basement membrane (GBM), in the presence of podocyte foot process effacement. Although previous studies indicate a prevalence of AS of about 1/50,000, a recent publication reported a predicted rate of pathogenic COL4A5 variants of 1/2320. We herewith present 98 patients (40 M/58 F) from 26 Greek families. We are selectively presenting the families segregating the X-linked form of AS with pathogenic variants in the COL4A5 gene. We found 21 different pathogenic variants, 12 novel: eight glycine and one proline substitutions in the collagenous domain, one cysteine substitution in the NC1 domain, two premature termination of translation codons, three splicing variants, one 5-bp insertion/frameshift variant, one indel-frameshift variant and four gross deletions. Notably, patients in six families we describe here and three families we reported previously, carried the COL4A5-p.G624D substitution, a founder defect encountered all over Europe which is hypomorphic with mostly milder symptomatology. Importantly, on several occasions, the correct genetic diagnosis reclassified patients as patients with AS, leading to termination of previous immunosuppressive/cyclosporine A therapy and a switch to angiotensin converting enzyme inhibitors (ACEi). With the understanding that all 98 patients span a wide range of ages from infancy to late adulthood, 15 patients (11 M/4 F) reached kidney failure and 11 (10 M/1 F) received a transplant. The prospects of avoiding lengthy diagnostic investigations and erroneous medications, and the advantage of delaying kidney failure with very early administration of renin-angiotensin-aldosterone system (RAAS) blockade, highlights the importance of timely documentation of AS by genetic diagnosis