title: A case report and literature review of Fanconi Anemia (FA) diagnosed by genetic testing.
abstract: Fanconi anemia (FA) is a genetically heterogeneous rare autosomal recessive disorder characterized by congenital malformations, hematological problems and predisposition to malignancies. The genes that have been found to be mutated in FA patients are called FANC. To date 16 distinct FANC genes have been reported. Among these, mutations in FANCA are the most frequent among FA patients worldwide which account for 60- 65%. In this study, a nine years old male child was brought to our hospital one year ago for opinion and advice. He was the third child born to consanguineous parents. The mutation analyses were performed for proband, parents, elder sibling and the relatives [maternal aunt and maternal aunt's son (cousin)]. Molecular genetic testing [targeted next-generation sequencing (MiSeq, Illumina method)] was performed by mutation analysis in 15 genes involved. Entire coding exons and their flanking regions of the genes were analysed. Sanger sequencing [(ABI 3730 analyzer by Applied Biosystems)] was performed using primers specific for 43 coding exons of the FANCA gene. A novel splice site mutation, c.3066 + 1G > T, (IVS31 + 1G > T), homozygote was detected by sequencing in the patient. The above sequence variant was identified in heterozygous state in his parents. Further, the above sequence variant was not identified in other family members (elder sibling, maternal aunt and cousin). It is concluded that genetic study should be done if possible in all the cases of suspected FA, including siblings, parents and close blood relatives. It will help us to plan appropriate treatment and also to select suitable donor for hematopoietic stem cell transplantation and to plan for genetic counseling. In addition to the case report, the main focus of this manuscript was to review literature on role of FANCA gene in FA since large number of FANCA mutations and polymorphisms have been identified.
authors.affiliation: Department of Paediatrics, Sree Balaji Medical College and Hospital, Chennai, 600 044, India. pjohnsolomon@yahoo.co.in.
authors.forename: Ponnumony John
authors.initials: PJ
authors.lastname: Solomon
authors.affiliation: Department of Paediatrics, Sree Balaji Medical College and Hospital, Chennai, 600 044, India. priya.ramita@gmail.com.
authors.forename: Priya
authors.initials: P
authors.lastname: Margaret
authors.affiliation: Department of Paediatrics, Sree Balaji Medical College and Hospital, Chennai, 600 044, India. priya.ramita@gmail.com.
authors.forename: Ramya
authors.initials: R
authors.lastname: Rajendran
authors.affiliation: Department of Physiology/Central research laboratory (CRL), Sree Balaji Medical College and Hospital, Chennai, 600 044, India. revybiomed@gmail.com.
authors.forename: Revathy
authors.initials: R
authors.lastname: Ramalingam
authors.affiliation: College of Applied Medical Sciences and Molecular Diagnostics and Personalised Therapeutics Unit (MDPTU), Ha'il University, Ha'il, Kingdom of Saudi Arabia (KSA). godfredmenezes@gmail.com.|Worked previously as in-charge and scientist in Central Research Laboratory (CRL), Sree Balaji Medical College and Hospital, Chennai, 600 044, India. godfredmenezes@gmail.com.
authors.forename: Godfred A
authors.initials: GA
authors.lastname: Menezes
authors.affiliation: Department of Paediatrics, Sree Balaji Medical College and Hospital, Chennai, 600 044, India. priya.ramita@gmail.com.
authors.forename: Alph S
authors.initials: AS
authors.lastname: Shirley
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea. sjlee0318@gmail.com.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea. mwseong@snu.ac.kr.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea. sparkle@snu.ac.k.
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea. sungimcho@gmail.com.
authors.forename: Dodam
authors.initials: D
authors.lastname: Seol
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea. shseo81@gmail.com.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Seo
mesh_terms: D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005199:Fanconi Anemia / Q000175:diagnosis* / Q000235:genetics*; D052217:Fanconi Anemia Complementation Group A Protein / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein