Open Access Highly Accessed Research article

Whole exome sequencing reveals concomitant mutations of multiple FA genes in individual Fanconi anemia patients

Lixian Chang12, Weiping Yuan12, Huimin Zeng12, Quanquan Zhou12, Wei Wei12, Jianfeng Zhou12, Miaomiao Li3, Xiaomin Wang12, Mingjiang Xu4, Fengchun Yang4, Yungui Yang3, Tao Cheng12* and Xiaofan Zhu12*

Author Affiliations

1 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

2 Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Beijing, China

3 Beijing Institute of Genomics, CAS, Beijing, China

4 Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA

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BMC Medical Genomics 2014, 7:24  doi:10.1186/1755-8794-7-24

Published: 15 May 2014



Fanconi anemia (FA) is a rare inherited genetic syndrome with highly variable clinical manifestations. Fifteen genetic subtypes of FA have been identified. Traditional complementation tests for grouping studies have been used generally in FA patients and in stepwise methods to identify the FA type, which can result in incomplete genetic information from FA patients.


We diagnosed five pediatric patients with FA based on clinical manifestations, and we performed exome sequencing of peripheral blood specimens from these patients and their family members. The related sequencing data were then analyzed by bioinformatics, and the FANC gene mutations identified by exome sequencing were confirmed by PCR re-sequencing.


Homozygous and compound heterozygous mutations of FANC genes were identified in all of the patients. The FA subtypes of the patients included FANCA, FANCM and FANCD2. Interestingly, four FA patients harbored multiple mutations in at least two FA genes, and some of these mutations have not been previously reported. These patients’ clinical manifestations were vastly different from each other, as were their treatment responses to androstanazol and prednisone. This finding suggests that heterozygous mutation(s) in FA genes could also have diverse biological and/or pathophysiological effects on FA patients or FA gene carriers. Interestingly, we were not able to identify de novo mutations in the genes implicated in DNA repair pathways when the sequencing data of patients were compared with those of their parents.


Our results indicate that Chinese FA patients and carriers might have higher and more complex mutation rates in FANC genes than have been conventionally recognized. Testing of the fifteen FANC genes in FA patients and their family members should be a regular clinical practice to determine the optimal care for the individual patient, to counsel the family and to obtain a better understanding of FA pathophysiology.

Fanconi anemia; Exome sequencing; DNA repair; Concomitant mutation