Diagnosis status and genetic characteristics analysis of Fanconi anemia in China
Li Niu, Hu Yixin, Qin Xia, Zhu Yiping, Zhou Ming, He Lan, Chang Lixian, Xu Xiaojun, Dai Yan, Cao Xingyu, Chen Kai, Wang Hongmei, Wang Chunjing, He Yuelin, Qian Xiaowen, Xu Lanping, Chen Jing
Abstract
ObjectiveTo analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China.
MethodsThe General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups.
ResultsOf the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185).
ConclusionsFANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Key words:
Fanconi anemia; Child; Genes; Chromosome breakage
Contributor Information
Li Niu
Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Hu Yixin
Department of Hematology, Children′s Hospital of Soochow University,Suzhou 215000, China
Qin Xia
Department of Hematology and Oncology, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Zhu Yiping
Department of Pediatrics, West China Second University Hospital of Sichuan University, Chengdu 610041, China
Zhou Ming
Department of Hematology, Guangzhou First People′s Hospital, Guangzhou 510030, China
He Lan
Nanfang-Chunfu Children′s Institute of Hematology &
Oncology, Dongguan 523000, China
Chang Lixian
Department of Pediatrics, Institute of Hematology &
Blood Diseases Hospital, Chinese Academy of Medical Sciences &
Peking Union Medical College, Tianjing 300020, China
Xu Xiaojun
Department of Hematology and Oncology, Children′s Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Dai Yan
Department of Pediatrics, People′s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China
Cao Xingyu
Department of Transplantation, Hebei Yanda Ludaopei Hospital, Langfang, 065201, China
Chen Kai
Department of Hematology and Oncology, Shanghai Children′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China
Wang Hongmei
Department of Pediatrics, the First Affiliated Hospital of Shandong First Medical University &
Shandong Provincial Qianfoshan Hospital, Jinan 250014, China
Wang Chunjing
Department of Hematology, Shenzhen Children′s Hospital, Shenzhen 518028, China
He Yuelin
Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Qian Xiaowen
Department of Hematology, Children′s Hospital of Fudan University, Shanghai 201102, China
Xu Lanping
Department of Hematology, Peking University People′s Hospital, Beijing 100044, China
Chen Jing
Department of Hematology and Oncology, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
