Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies

Abstract

Background Fanconi anemia (FA) is the most common inherited bone marrow failure (BMF) syndrome with 22 related genes identified. The ALDH2 rs671variant has been proved related to accelerated progression of BMF in FA patients. The phenotype and genetic basis of Chinese FA patients have not been investigated yet.Methods We analyzed the 22 FA-related genes of 63 BMF patients suspected to be FA. Clinical manifestations, morphological and cytogenetic feathers, ALDH2 genotypes, treatment, and outcomes of the definite cases were retrospectively studied.Results 24 patients were confirmed the diagnosis of FA. The median age of BMF onset was 4.5-year old. The number of patients manifested as congenital malformations and growth retardation were 21/24 and 14/24, respectively. BM dysplasia and cytogenetic abnormalities were found in 15/23 and 10/22 patients. All the patients with abnormal karyotype also manifested as BM dysplasia or had evident blasts. Thirty-nine different variants were identified involving seven genes and including twenty-one novel variants. FANCA variants contributed to 58.33% of cases. Ten patients carried ALDH2 -G/A genotype with a significantly younger age of BMF onset ( p =0.024). Within the 22 patients adhering to continuous follow-up, 18 patients underwent hematopoietic stem cell transplantations (HSCTs). During the 33.5 months of follow-up, 8/22 patients died, seven of which were HSCT-related, and one patient who didn’t receive HSCT died from severe infection.Conclusion The phenotypic and genetic spectrum of Chinese FA patients is broad. Bone marrow dysplasia and cytogenetic abnormalities are prevalent and highly consistent. The overall outcome of HSCTs is disappointing. Nationwide multicenter studies are needed for the rarity and adverse outcome of this disease.

Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction

“…Our sensors provide a toolkit that may help to improve our understanding of the potential roles of FA in various cellular processes. Some recent research examined Fanconi anemia patients and found that people holding the ALDH2 dominant-negative variant (ALDH2*2) had the tendency of accelerated progression of bone marrow failure (BMF) 48,49 . Study on Fancd2, Aldh2 and Adh5 knockout mice have indicated the effect of increased endogenous formaldehyde in the process 4,5 .…”