A novel frame-shift deletion in FANCF gene causing autosomal recessive Fanconi anemia: a case report

Abstract

Background Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by congenital anomalies, early-onset bone marrow failure, and a high predisposition to cancers. Up to know, different genes involved in the DNA repair pathway, mainly FANCA genes, have been identified to be affected in patients with FA. Case presentation Here, we report clinical, laboratory and genetic findings in a 3.5-year-old Iranian female patient, a product of a consanguineous marriage, who was suspicious of FA, observed with short stature, microcephaly, skin hyperpigmentation, anemia, thrombocytopenia and hypo cellular bone marrow. Therefore, Next Generation Sequencing was performed to identify the genetic cause of the disease in this patient. Results revealed a novel, private, homozygous frameshift mutation in the FANCF gene (NM_022725: c. 534delG, p. G178 fs) which was confirmed by Sanger sequencing in the proband. Conclusion Such studies may help uncover the exact pathomechanisms of this disorder and establish the genotype-phenotype correlations by identification of more mutations in this gene. It is the first report of a mutation in the FANCF gene in Iranian patients with Fanconi anemia. This new mutation correlates with a hematological problem (pancytopenia), short stature, and microcephaly and skin hyperpigmentation. Until now, no evidence of malignancy was detected. Electronic supplementary material The online version of this article (10.1186/s12881-019-0855-2) contains supplementary material, which is available to authorized users.

Higher burden of rare frameshift indels in genes related to synaptic transmission separate familial hemiplegic migraine from common types of migraine

“…33–35 Frameshift indels can also act in a recessive way, where an accumulation of frameshift indels is necessary to induce a certain phenotype. 36 Our results indicate that FHM in patients without a mutation in CACNA1A , ATP1A2 and SCN1A is possibly caused by an accumulation of rare frameshift indels in multiple genes. This would mean that FHM is not always a dominantly inherited monogenic disease but is caused by the interaction of mutations in multiple genes with moderate effects.…”

“…In rare cases, such proteins can, in an autosomal-dominant way, induce severe phenotypes, including neurological diseases 33–35. Frameshift indels can also act in a recessive way, where an accumulation of frameshift indels is necessary to induce a certain phenotype 36. Our results indicate that FHM in patients without a mutation in CACNA1A , ATP1A2 and SCN1A is possibly caused by an accumulation of rare frameshift indels in multiple genes.…”

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

“…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.…”

Novel FANCA mutation in the first fully-diagnosed patient with Fanconi anemia in Polish population – case report

“…Patients struggle with progressive bone marrow failure and severe hematological complications [24]. In addition, congenital malformations are also present [25,26]. All of these have been reported as germline mutations, resulting in an in-frame deletion of phenylalanine at a position that is conserved across species.…”

“…Patients struggle with progressive bone marrow failure and severe hematological complications [ 24 ]. In addition, congenital malformations are also present [ 25 , 26 ].…”