Phenotypic and genotypic correlation evaluation of 148 pediatric patients with Fanconi anemia in a Chinese rare disease cohort.

Fanconi anemia (FA) is a rare autosomal recessive, X-linked or autosomal dominant disease. Few large-scale FA investigations of rare disease cohorts have been conducted in China. We enrolled 148 patients diagnosed with FA according to evidence from the clinical phenotype, family history, and a set of laboratory tests. Next, the clinical manifestations and correlation between the genotype and phenotype of FA pediatric cases were investigated. The most common FA subtype in our cohort was FA-A (51.4 %), followed by FA-D2 and FA-P. Finger (26 %) and skin (25 %) deformities were the most common malformations. Based on family history, blood system diseases (51 %) had the highest incidence rate, followed by digestive system tumours. A set of new or prognosis-related mutation sites was identified. For example, c.2941 T > G was a new most common missense mutation site for FANCA. FANCP gene mutation sites were mainly concentrated in exons 12/14/15. The mutations of FANCI/FANCD2 were mainly located at the α helix and β corners of the protein complex. FA-A/D1 patients with splicing or deletion mutations showed more severe disease than those with missense mutations. Chromosome 1/3/7/8 abnormalities were closely linked to the progression of FA to leukemia. Our study investigated the clinical features and genotype/phenotype correlation of 148 Chinese pediatric FA patients, providing new insight into FA. [ABSTRACT FROM AUTHOR]