👤 B Peterlin

Venous thromboembolism (VTE) are rare but potentially life-threatening conditions in children, usually associated with underlying medical conditions. Some children with diagnosed VTE have genetic risk factors for the development of VTE, as well as for recurrent complications. This study reports risk factors for developing VTE in a homogeneous population of children and adolescents. A total of 155 children and adolescents, aged 0-21 years, who were diagnosed with VTE at the University Children's Hospital, UMC Ljubljana, between July 2006 and October 2021, were included. The median age at the time of the VTE diagnosis was 12.0 years (interquartile range: 1-7 years). Associated medical conditions were present in 75.5% of patients, and thrombophilia was diagnosed in 43.2% of patients. Oncological disease accounted for 27.7% of cases, while infections were found to be the most significant acquired risk factor (17.4%), followed by the presence of a central venous catheter (15.5%). Genetic thrombophilia markers were identified in 27.1% of patients, with the highest frequency in adolescents (62.5%). Factor V (FV) Leiden heterozygote was the most common marker (9.6% of patients), followed by elevated factor VIII (FVIII) activity (5.8%) and elevated Lp(a) levels (5.2%). Combined thrombophilia markers were found in 52.2% of patients. In addition to inherited thrombophilia, 83.3% of patients had acquired risk factors. Compared to previously reported prevalence, a lower occurrence of FV Leiden heterozygote, elevated Lp(a) levels, elevated FVIII activity and antiphospholipid syndrome was observed in our population. Show less

Hypertrophic cardiomyopathy is often caused by pathogenic MYBPC3 variants. The study of Italian patients with HCM and MYBPC3(NM₀₀₀₂₅₆.3):c.913₉₁₄del showed a higher disease penetrance in males and a higher frequency of arrhythmias compared to patients with other likely pathogenic and pathogenic (LP/P) MYBPC3 variants. We investigated the clinical outcomes of Slovenian probands with MYBPC3 LP/P variants, estimated the variant penetrance and compared the results with an Italian study. We identified 31 haplotype-matched individuals with MYBPC3:c.913₉₁₄del and 34 individuals with other LP/P MYBPC3 variants. We observed some significant differences in clinical and echocardiographic characteristics and frequency of adverse cardiac events between Slovenian and Italian probands with MYBPC3:c913₉₁₄del. We were unable to replicate previous findings for MYBPC3:c.913₉₁₄del, highlighting the complexity of genotype-phenotype associations. Show less

In the March issue of the Journal in 2012, we reported on a girl with Langer-Giedion syndrome (LGS) phenotype and a 7.5 Mb interstitial deletion at 8q23.3q24.13, encompassing the EXT1, but not the TRPS1 gene. Recent discoveries have shown that heterozygous intragenic mutations or contiguous gene deletions including the RAD21 gene, which is located downstream of the TRPS1 gene, are the cause of Cornelia de Lange syndrome-4. Considering that the interstitial deletion in our patient included the RAD21 and 30 other RefSeq genes, we would like to suggest a revision of the diagnosis reported in our previous paper and compare our patient to other reported patients with Cornelia de Lange syndrome-4 caused by heterozygous deletions of chromosome 8q24. © 2015 Wiley Periodicals, Inc. Show less

Langer-Giedion syndrome (LGS) is a contiguous gene syndrome caused by a hemizygous deletion on chromosome 8q23.3-q24.11 involving TRPS1 and EXT1 genes. We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3-q24.13. Array-comparative genomic hybridization (a-CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarche classified as Tanner stage 3 premature pubarche which have not yet been described as features of LGS. We examine the molecular breakpoints and phenotypes of our patient and previously reported cases. Show less

High frequencies of loss of heterozygosity (LOH) in chromosome 11q22-qter have been observed in various malignancies, including breast cancer. Previous studies on breast carcinomas by Winqvist et al (Cancer Res 55: 2660-2664) have indicated that a survival factor gene is located in band 11q23, and that the highly informative microsatellite polymorphism at the APOC3 locus would be a suitable tool to perform more extensive LOH studies. In this European multicentre study, we have examined the occurrence of APOC3 LOH and evaluated the effect of LOH of this chromosomal subregion on the clinical behaviour of the disease in a cohort of 766 breast cancer patients in more detail. LOH for APOC3 was found in 42% of the studied tumours, but it was not found to be significantly associated with any of the studied clinical variables, including cancer-specific survival time or survival time after recurrent/metastatic disease. According to the present findings, the putative survival factor gene on 11q23 is not located close enough to the APOC3 gene, but apparently at a more proximal location. Show less