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Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder, particularly present in the Mediterranean populations, and associated with pathogenic variants in the MEFV gene. This study aims to investigate the distribution of MEFV variants in a large cohort of Lebanese patients, and to explore the genotype-phenotype correlation among affected individuals. A retrospective analysis was conducted on 3,167 patients referred for MEFV sequencing at the Medical Genetics and Genomics Center(CGGM) at Saint-Joseph University of Beirut-Lebanon, from 2006 to 2023. Sanger sequencing was used to detect MEFV variants, focusing initially on hot-spot exons. Among the 3,167 patients, 46.73% (N = 1,480) carried at least one MEFV variant. The most common variants detected were M694V and V726A, both found in 28.98% of cases, followed by E148Q(27.83%) and M694I(13.98%). Moreover, Shiites and Sunni Muslims, and individuals from South and North Lebanon exhibited the highest frequency of variants. Interestingly, family history was found to be significantly higher in patients having two MEFV variants than those with one variant (p = 0.0026). The most commonly reported symptoms were fever(78%), abdominal pain(88%), joint pain(65%), and thoracic pain(46%). The genotype-phenotype correlation analysis revealed a more severe phenotype in patients carrying the M694V or V726A mutations compared to those with the homozygous E148Q genotype. This study, the largest in Lebanon, highlights the high prevalence of MEFV variants, particularly M694V and V726A, in FMF patients. Our data provide valuable insights into the genetic landscape of FMF in Lebanon and emphasize the importance of early genetic screening for a better disease management and genetic counselling.

White-Sutton Syndrome (WHSUS) is a rare neurodevelopmental genetic disorder with an autosomal dominant mode of inheritance. Truncating mutations in pogo transposable element with zinc finger domain (POGZ) gene have been reported in cases of WHSUS. In this article, we present the first diagnosed case of WHSUS in Lebanon. The 10-month-old infant presented with failure to thrive, chronic diarrhea, vomiting and recurrent upper respiratory tract infections. Molecular testing was performed showing a novel nonsense variant in the POGZ gene: c.1135C > T p.(Arg379∗). With a relatively mild form of the disease, our findings suggest that WHSUS patients may present heterogenous clinical features.

Conventional cytogenetic analysis is an important tool for the diagnosis of many hematologic disorders (HD). A karyotype is designed as « complex » when several alterations are detected. However, there is no clear consensus on the exact definition of a complex karyotype (CK), and there is a lack of studies that exclusively analyze CK in the literature. Complex karyotypes were analyzed over a period of 12 years at the Jacques Loiselet Center for Medical Genetics and Genomics (CGGM) at Saint Joseph University in Beirut (USJ) in Lebanon. 255 CK were analyzed with their associated chromosomal abnormalities (CA) detected. Out of 255 patients, 59.22% were males with a mean age of 59 years. The most common anomaly associated with CK was hyperdiploidy with a prevalence of 22.41%, which is different from a previously published study. To our knowledge, this represents the largest series of CK, particularly within the Middle East region. This study underscores the critical role of conventional cytogenetics in detecting CK, ultimately contributing to improved management of HD. Further investigations focusing on CK are needed.

Mutated or unmutated immunoglobulin heavy chain (IGHV) gene is an important prognostic factor in chronic lymphocytic leukemia (CLL). However, a small fraction of patients with CLL are classified as borderline (BL)-IGHV. Few data are available on this subgroup of CLL. In this paper, we retrospectively report and analyze data from 21 patients with BL-IGHV CLL, showing the heterogeneity of this subgroup of CLL and paving the way for more research focusing on this entity to optimize the management and treatment of patients with Borderline-IGHV CLL.

Abstract Cancer is one of the foremost causes of mortality. The human genome remains stable over time. However, human activities and environmental factors have the power to influence the prevalence of certain types of mutations. This goes to the excessive progress of xenobiotics and industrial development that is expanding the territory for cancers to develop. The mechanisms involved in immune responses against cancer are widely studied. Genome editing has changed the genome‐based immunotherapy process in the human body and has opened a new era for cancer treatment. In this review, recent cancer immunotherapies and the use of genome engineering technology are largely focused on.

Cutaneous T‐cell lymphomas (CTCLs) are telomerase‐positive tumors expressing hTERT, although neither gene rearrangement/amplification nor promoter hotspot mutations could explain the hTERT re‐expression. As the hTERT promoter is rich in CpG, we investigated the contribution of epigenetic mechanisms in its re‐expression. We analyzed hTERT promoter methylation status in CTCL cells compared with healthy cells. Gene‐specific methylation analyses revealed a common methylation pattern exclusively in tumor cells. This methylation pattern encompassed a hypermethylated distal region from −650 to −150 bp and a hypomethylated proximal region from −150 to +150 bp. Interestingly, the hypermethylated region matches with the recently named TERT hypermethylated oncogenic region (THOR). THOR has been associated with telomerase reactivation in many cancers, but it has so far not been reported in cutaneous lymphomas. Additionally, we assessed the effect of THOR on two histone deacetylase inhibitors (HDACi), romidepsin and vorinostat, both approved for CTCL treatment and a DNA methyltransferase inhibitor (DNMTi) 5‐azacytidine, unapproved for CTCL. Contrary to our expectations, the findings reported herein revealed that THOR methylation is relatively stable under these epigenetic drugs' pressure, whereas these drugs reduced the hTERT gene expression.

Abstract Background Telomere shortening is linked to a range of different human diseases, hence reliable measurement methods are needed to uncover such associations. Among the plethora of telomere length measurement methods, qPCR is reported as easy to conduct and a cost‐effective approach to study samples with low DNA amounts. Methods Cancer cells’ telomere length was evaluated by relative and absolute qPCR methods. Results Robust and reproducible telomere length measurements were optimized taking into account a careful reference gene selection and by knowing the cancer cells ploidy. qPCR data were compared to “gold standard” measurement from terminal restriction fragment (TRF). Conclusions Our study provides guidance and recommendations for accurate telomere length measurement by qPCR in cancer cells, taking advantage of our expertise in telomere homeostasis investigation in primary cutaneous T‐cell lymphomas. Furthermore, our data emphasize the requirement of samples with both, high DNA quality and high tumor cells representation.

Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL) in which the human Telomerase Reverse Transcriptase (hTERT) gene is re-expressed. Current available treatments do not provide long-term response. We previously reported that Histone deacetylase inhibitors (HDACi, romidespin and vorinostat) and a DNA methyltransferase inhibitor (DNMTi, 5-azacytidine) can reduce hTERT expression without altering the methylation level of hTERT promoter. Romidepsin and vorinostat are approved for CTCL treatment, while 5-azacytidine is approved for the treatment of several hematological disorders, but not for CTCL. Here, using the soft agar assay, we analyzed the functional effect of the aforementioned epidrugs on the clonogenic capacities of Sézary cells. Our data revealed that, besides hTERT downregulation, epidrugs’ pressure reduced the proliferative and the tumor formation capacities in Sézary cells in vitro.

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. Chromosomal abnormalities are reported to play important roles in CLL pathogenesis and evolution, including deletions of 11q, 13q, 17p, and trisomy12, that are frequently observed and have a known prognostic value. Furthermore, the mutational status of the IGHV gene was reported as an independent prognostic marker in CLL impacting the choice of therapy. We herein, report an unusual presentation of a Lebanese CLL patient with two cytogenetic abnormalities: trisomy 12 and t(14;18)(q32;q21), along with an unmutated IGHV, displaying a favorable response to ibrutinib with a maintained complete remission.

Acute myeloid leukemia (AML) patients with MLL-SEPT6 fusion represent a small subset of AML. The uncommon MLL-SEPT6 rearrangement results from t(X;11) or other variants like ins(X;11), and it is usually associated with complex cytogenetic abnormalities. We herein report a case of AML-M5-infant with ins(X;11)(q24;q23q13) and MLL-SEPT6. The one-year-old boy presented with leukocytosis, anemia and thrombocytopenia. He had a favorable response to chemotherapy according to ELAM02protocol and is currently in complete remission. We here, highlight the occurrence of MLL-SEPT6 as the sole abnormality in a pediatric-AML-M5 case, discuss the prognostic implication of this genetic variant, while reviewing previously reported AML-MLL-SEPT6 cases.

Abstract Background Cockayne Syndrome (CS) is a rare autosomal recessive disorder characterized by neurological and sensorial impairment, dwarfism, microcephaly and photosensitivity. CS is caused by mutations in ERCC6 (CSB) or ERCC8 (CSA) genes. Methods Three patients with CS were referred to the Medical Genetics Unit of Saint Joseph University. Sanger sequencing of both ERCC8 and ERCC6 genes was performed: ERCC8 was tested in all patients while ERCC6 in one of them. Results Sequencing led to the identification of three homozygous mutations, two in ERCC8 (p.Y322* and c.843 + 1G > C) and one in ERCC6 (p.R670W). All mutations were previously reported as pathogenic except for the c.843 + 1G > C splice site mutation in ERCC8 which is novel. Conclusions Molecular diagnosis was established in all patients included in our study. A genotype-phenotype correlation is discussed and a link, between mutations and some specific religious communities in Lebanon, is suggested.

Acute myeloid leukemia (AML) is characterized by chromosomal abnormalities affecting both prognosis and course of treatment. While most AML patients have well described chromosomal aberrations, around 10% present with rare chromosomal abnormalities.We herein, report a rare balanced translocation t(12;19)(q13;q13) in a 66-year old M5-AML patient identified by Conventional cytogenetic analysis and confirmed by SNP array. We suggest that t(12;19) as a sole chromosomal abnormality could be associated with a poor prognosis. Further studies are needed to understand the molecular basis of this translocation in AML.