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Loss or decrease of function in runt-related transcription factor 2 encoded by RUNX2 is known to cause a rare autosomal-dominant skeletal disorder, cleidocranial dysplasia (CCD). Clinical spectrum and genetic findings in 51 CCD patients from 30 unrelated families are herein presented. In a majority of the patients, facial abnormalities, such as delayed fontanel closure (89%), parietal and frontal bossing (80%), metopic groove (77%), midface hypoplasia (94%), and abnormal mobility of shoulders (90%), were recorded following clinical examination. In approximately one-half of the subjects, wormian bone (51%), short stature (43%), bell-shaped thorax (42%), wide pubic symphysis (50%), hypoplastic iliac wing (59%), and chef's hat sign (44%) presented in available radiological examinations. Scoliosis was identified in 28% of the patients. Investigation of RUNX2 revealed small sequence alterations in 90% and gross deletions in 10% of the patients; collectively, 23 variants including 11 novel changes (c.29_30insT, c.203delAinsCG, c.423 + 2delT, c.443_454delTACCAGATGGGAinsG, c.505C > T, c.594_595delCTinsG, c.636_637insC, c.685 + 5G > A, c.1088G > T, c.1281delC, Exon 6-9 deletion) presented high allelic heterogeneity. Novel c.29_30insT is unique in affecting the P1-driven long isoform of RUNX2, which is expected to disrupt the N-terminal region of RUNX2; this was shown in two unrelated phenotypically discordant patients. The clinical findings highlighted mild intra-familial genotype-phenotype correlation in our CCD cohort.

Multiple myeloma (MM) is a disease in which plasma cells increase clonally. We aimed to investigate the comparison of our transcriptome data in MM, MGUS (Monoclonal gammopathy of undetermined significance) and control groups in our research. Analysis of transcriptome data revealed that CD74, FUS, MS4A3, PTPN6, PRDX5 and UNC45B genes were significantly different in the MM group compared to control group. Pathway analyzes of these genes have shown that they are associated with certain pathways such as the cellular response and immunological system. In this study, we aimed to examine the expression levels of these genes among the MM (n=50), MGUS (n=15) and control (n=14) groups using the Quantitative Real-Time Polymerase Chain Reaction. According to the consequence of the study, it was determined that MS4A3 gene expression decreased significantly in the MM patient group compared to MGUS and control group, while PRDX5 gene expression was significantly increased. Also ROC (Receiver Operating Characteristic) analysis showed that MS4A3 gene has a significant diagnostic power between MM and MGUS group (area=0.727; p=0.008). Since multiple myeloma is more common in men than in women, it was statistically evaluated whether there is no difference in gene expression between women and men. However, it was determined that there was no statistically significant difference between the groups. As a result, the MS4A3 and PRDX5 genes, which are important in various diseases such as cancer, may shed light on new treatment options for MM disease. WOS:000708227600002 Q4

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.

Svrha rada bila je ispitati genetsku nestabilnost limfocita iz perifernog krvotoka primjenom razmjene sestrinskih kromatida (SCE-a) kod pacijenata sa Sjögrenovim sindromom (SS-om). Pacijenti i metode: ispitano je koliko je čest SCE (po metafazi) kod pacijenata s primarnim Sjögrenovim sindromom (n=30), zatim kod neliječenih pacijenata (n=15) i među zdravim pojedincima (n=15) u kontrolnim skupinama. Rezultati: vrijednosti srednje učestalosti SCE-a koje smo dobili za pacijente sa SSom, kod onih s neliječenim limfomom i kod zdravih u kontrolnoj skupini, iznosile su 7,77±1,50, 8,80±0,75 i 6,65±1,50. Dobili smo statistički znatne razlike između pacijenata sa SS-om i onih s limfomom (p=0,007) te između pacijenata s limfomom i zdravih sudionika iz kontrolnih skupina (p=0,0001). Nisu zapažene statistički velike razlike između pacijenata sa SS-om i onih u kontrolnim skupinama, s obzirom na srednju čestoću SCE-a (po metafazi). Zaključak: poznato je da se kod oko pet posto svih pacijenata sa SS-om mogu razviti limfomi. Česti SCE smatra se citogenetskim biomarkerom ranoga mutagenog učinka koji upućuje na povećani rizik od raka. Uočili smo da su vrijednosti srednje učestalosti razmjene sestrinskih kromatida (po metafazi) kod triju pacijenata sa SS-om bile više u odnosu prema vrijednostima ustavnovljenima kod pacijenata s neliječenim limfomom. Rezultat se može provjeriti procjenom drugih parametara s važnom zadaćom u malignoj transformaciji., Purpose: To investigate genomic instability by using Sister Chromatid Exchange (SCE) in the peripheral blood lymphocytes in patients with Sjögren’s syndrome (SS). Patients and Methods: The frequency of SCE (per metaphase) was investigated in patients with primary Sjögren’s Syndrome (n=30), in untreated lymphoma patients (n=15) and healthy individuals (n=15) who constitute the control groups. Results: We found the mean frequencies of SCE in the patients with SS, untreated lymphoma and healthy controls as 7.77±1.50, 8.80±0.75, 6.65±1.50, respectively. We found statistically significant differences between patients with SS and lymphoma (p=0.007) and also between patients with lymphoma and healthy controls (p=0.0001). No significant difference was observed between patients with SS and healthy controls in regard of mean frequencies of SCE (per metaphase). Conclusion: It is well known that up to 5.0% of all SS patients may develop lymphoma. High frequency of SCE is regarded as a cytogenetic biomarker of early mutagenic effect suggesting increased risk of cancer. We observed that the mean frequencies of sister chromatid exchanges (per metaphase) of three patients with SS were higher than those of untreated lymphoma patients. This result can only be verified by prolonged follow-up of these patients. We suggest that results should be interpreted by evaluating other parameters which play important roles in malignant transformation.