Screening for mutations in two exons of FANCG gene in Pakistani population

Aymun, Ujala; Iram, Saima; Aftab, Iram; Khaliq, Saba; Ali, Nadir; Ahmed, Nisar; Mohsin, Shahida

doi:10.5507/bp.2017.030

Cited by 8 publications

(6 citation statements)

References 46 publications

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“…There have been a limited number of reports on the genetic etiology of FA in populations from South Asia and the Middle East. Such studies have identified several novel disease‐causing germline genetic variants, including the first reports of FA caused by pathogenic variants in FANCO / RAD51C or FANCE (Aftab et al, 2017 ; Aslan et al, 2015 ; Aymun et al, 2017 ; Balta et al, 2000 ; Castella et al, 2011 ; de Winter et al, 2000 ; Donovan et al, 2019 ; Dorsman et al, 2007 ; Esmail Nia et al, 2016 ; Ghazwani et al, 2016 ; Gille et al, 2012 ; Kalb et al, 2007 ; Koc et al, 1999 ; Levran et al, 1997 ; Moghadam et al, 2016 ; Salem et al, 2014 ; Shahid et al, 2019 ; Shamseldin et al, 2012 ; Shukla et al, 2013 ; Solanki et al, , 2016 , 2017 ; Tamary et al, , 2000 , 2004 ; Vaz et al, 2010 ; Vundinti, 2014 ; Waisfisz et al, 1999 ; Wegner et al, 1996 ; Wijker et al, 1999 ; Zareifar et al, 2019 ) as well as discovery of a founder mutation in FANCL (Donovan et al, 2019 ), highlighting the importance of germline genetic studies of FA in underrepresented regions. In this report, we evaluated the genetic causes of FA in 19 patients from 17 unrelated families being considered for HCT in Pakistan and conducted a detail review of the causes of FA in South Asia and the Middle East.…”

Section: Introductionmentioning

confidence: 99%

The causes of Fanconi anemia in South Asia and the Middle East: A case series and review of the literature

Thompson

Saba

McReynolds

et al. 2021

Molec Gen & Gen Med

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Background Fanconi anemia (FA) is an inherited bone marrow failure syndrome associated with characteristic dysmorphology primarily caused by biallelic pathogenic germline variants in any of 22 different DNA repair genes. There are limited data on the specific molecular causes of FA in different ethnic groups. Methods We performed exome sequencing and copy number variant analyses on 19 patients with FA from 17 families undergoing hematopoietic cell transplantation evaluation in Pakistan. The scientific literature was reviewed, and we curated germline variants reported in patients with FA from South Asia and the Middle East. Results The genetic causes of FA were identified in 14 of the 17 families: seven FANCA, two FANCC, one FANCF, two FANCG, and two FANCL. Homozygous and compound heterozygous variants were present in 12 and two families, respectively. Nine families carried variants previously reported as pathogenic, including two families with the South Asian FANCL founder variant. We also identified five novel likely deleterious variants in FANCA, FANCF, and FANCG in affected patients. Conclusions Our study supports the importance of determining the genomic landscape of FA in diverse populations, in order to improve understanding of FA etiology and assist in the counseling of families.

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Section: Introductionmentioning

confidence: 99%

The causes of Fanconi anemia in South Asia and the Middle East: A case series and review of the literature

Thompson

Saba

McReynolds

et al. 2021

Molec Gen & Gen Med

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“…The age at diagnosis is approximately 7 years, which is indicative of the delay in diagnosis. Physicians often dissociate malformations from haematological damage, which leads to the misdiagnosis [9]. In our patient, haematological damage led us to the diagnosis.…”

Section: Introductionmentioning

confidence: 63%

“…Although the presentation is classic, we note a diagnostic delay in our patients. The median age of onset is 7-year-old [9]. This is related on the one hand to the fact that the orthopaedic abnormalities hide the anaemia and the care were focused on surgery; and on the other hand, the difficulties in typing anaemia because of previous transfusions and many iron supplementations.…”

Section: Discussionmentioning

confidence: 99%

From Surgery to Hematology: Fanconi Anemia about a Case of a Senegalese Child

Kane¹,

Deme-Ly²,

Diagne³

et al. 2020

OJPed

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Fanconi anaemia (FA) is a rare genetic abnormality. Most of FA reported from the sub-Saharan population came from southern Africa, with many patients linked to a mutation in the FANC G gene. Classic triads of this disorder are: a varied malformation, bone marrow failure, and short stature. This disorder is also associated with predisposition to malignancies. These multiple manifestations, sometimes not uniform, often cause diagnostic delay. We here report a 13-year-old Senegalese boy with FA. He was followed up for polydactyly-repair surgery. Importantly, pre-operative blood checkup revealed severe anaemia, which prompted us to perform bone marrow aspiration: examination revealed dysmyelopoiesis. Being triggered by this, systematic examinations were performed, which revealed other signs indicative of FA; i.e., radial spine abnormalities, triangular face, etc. The diagnosis of FA was strongly suggested, which prompted genetic examination. The chromosomal breakage test detected cellular hypersensitivity to DNA, which confirmed the diagnosis. He is receiving transfusion support, and androgens use is being considered. This case highlights the importance of preoperative examination. Physicians must be aware that FA, although its incidence is low, can be hidden behind infantile anaemia.

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“…And the lack of FANCA and FANCG expression was also associated with these two sporadic cancers 47 . The FANCG gene mutation is the third most common type of FA mutation 48 . FANCG and HR also have a certain functional relationship, and FANCG inactivation will reduce HR repair function 49 …”

Section: Discussionmentioning

confidence: 99%

The identification of six risk genes for ovarian cancer platinum response based on global network algorithm and verification analysis

Xing

Zhang

et al. 2020

J Cellular Molecular Medi

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Ovarian cancer is the most lethal gynaecological cancer, and resistance of platinum‐based chemotherapy is the main reason for treatment failure. The aim of the present study was to identify candidate genes involved in ovarian cancer platinum response by analysing genes from homologous recombination and Fanconi anaemia pathways. Associations between these two functional genes were explored in the study, and we performed a random walk algorithm based on reconstructed gene‐gene network, including protein‐protein interaction and co‐expression relations. Following the random walk, all genes were ranked and GSEA analysis showed that the biological functions focused primarily on autophagy, histone modification and gluconeogenesis. Based on three types of seed nodes, the top two genes were utilized as examples. We selected a total of six candidate genes (FANCA, FANCG, POLD1, KDM1A, BLM and BRCA1) for subsequent verification. The validation results of the six candidate genes have significance in three independent ovarian cancer data sets with platinum‐resistant and platinum‐sensitive information. To explore the correlation between biomarkers and clinical prognostic factors, we performed differential analysis and multivariate clinical subgroup analysis for six candidate genes at both mRNA and protein levels. And each of the six candidate genes and their neighbouring genes with a mutation rate greater than 10% were also analysed by network construction and functional enrichment analysis. In the meanwhile, the survival analysis for platinum‐treated patients was performed in the current study. Finally, the RT‐qPCR assay was used to determine the performance of candidate genes in ovarian cancer platinum response. Taken together, this research demonstrated that comprehensive bioinformatics methods could help to understand the molecular mechanism of platinum response and provide new strategies for overcoming platinum resistance in ovarian cancer treatment.

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Screening for mutations in two exons of FANCG gene in Pakistani population

Cited by 8 publications

References 46 publications

The causes of Fanconi anemia in South Asia and the Middle East: A case series and review of the literature

The causes of Fanconi anemia in South Asia and the Middle East: A case series and review of the literature

From Surgery to Hematology: Fanconi Anemia about a Case of a Senegalese Child

The identification of six risk genes for ovarian cancer platinum response based on global network algorithm and verification analysis

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