Iranian journal of Pediatric Hematology and Oncology

en Unveiling the Clinicopathological and Molecular Spectrum of Fanconi Anaemia: Insights from a Single-Centre Experience. ژنتیک Genetics پژوهشي Research  Background: Fanconi anaemia (FA) is the most common cause of constitutional bone marrow failure. The pathophysiology of this disease is highly complex and still unclear. It is caused by a mutation/pathogenic variant in any of the 22 complementation groups that work together in the DNA damage repair mechanism. Approximately three-fourths of FA cases are due to defects in the FANCA gene. This study investigates the molecular and clinicopathological profiles of FA patients. Materials and Methods: This prospective observational study screened 780 aplastic anaemia patients using chromosomal breakage analysis, and the results were positive for 60 patients, therefore labeled as FA. Baseline biodata and clinical and laboratory parameters were recorded via a questionnaire. In this study, Samples from the first 50 patients were screened for c.378803790delTCT through PCR RFLP, which revealed its presence in one patient. Ten additional samples were also screened via next-generation sequencing (NGS) for broader genetic analysis. Results: The median age of the patients was 11.5 years (IQR 5 years), with the majority (68%) of the participants being male. Growth retardation and pancytopenia were present in 98.3% and 95% patients, respectively. A total of 20 variants were detected (2 via RFLP and 18 via NGS). Seventeen were pathogenic variants, of which 16 (80%) affected FANCA and 20% affected FANCG. Twelve variants (74%) in FANCA were deletions. c.3788-3790delTCT was detected in 3 out of 60 patients (1 through RFLP and the other 2 through NGS). Conclusion: FA is a clinically and genetically heterogeneous disease. Patients presenting with cytopenia combined with growth retardation and somatic abnormalities should be suspected of having FA. Genetic diagnosis is necessary for confirmation. NGS can aid in the diagnosis and subtyping of patients in whom targeted/hotspot mutations are unknown. Fanconi anemia, FANCA, genetic analysis, inherited marrow failure, next generation sequencing. 858 867 http://ijpho.ssu.ac.ir/browse.php?a_code=A-10-671-1&slc_lang=en&sid=1 Saima Siddiqui Saima Siddiqui Saimee_80@yahoo.com 0000-0001-5178-937X Yes NIBD AND BMT HOSPITAL National Institute of Blood diseases and Bone Marrow Transplantation, PECHS campus Ikram din Ujjan Ikram din Ujjan ikramuhhan@lumhs.edu.pk No Liaquat University of Medical and Health Sciences Liaquat University of Medical and Health Sciences shariq AHMED shariq AHMED shariq.nibd@gmail.com No NIBD AND BMT HOSPITAL National Institute of Blood diseases and Bone Marrow Transplantation, PECHS campus Danish Zahid Danish Zahid danishzahid69@yahoo.com No National Institute of Blood diseases and Bone Marrow Transplantation, PECHS campus National Institute of Blood diseases and Bone Marrow Transplantation, PECHS campus Safia mehmood khan Safia mehmood rphsafia.nibd@Gmail.com No National Institute of Blood diseases and Bone Marrow Transplantation, PECHS campus National Institute of Blood diseases and Bone Marrow Transplantation, PECHS campus affaf sheikh affaf sheikh rphaffaf12@gmail.com No National Institute of Blood diseases and Bone Marrow Transplantation, PECHS campus National Institute of Blood diseases and Bone Marrow Transplantation, PECHS campus Ali Waryah Ali Waryah aliwaryah@hotmail.com No Liaquat University of Medical and Health Sciences Liaquat University of Medical and Health Sciences