A Pedigree Study Of Congenital Sideroblastic Anemia Caused By NDUFB11 Gene Mutation

Objective:Congenital sideroblastic anemia（CSA）is a rare congenital anemia characterized by loss of iron utilization and presence of ring sideroblasts in bone marrow.It is known that CSA is closely related to a variety of gene mutations,including autosomal recessive,X-chromosome and so on.A patient with CSA and his pedigree were studied in order to determine the pathogenic gene,explore the pathogenesis and treatability,and provide the optimal individualized diagnosis and treatment strategy for the whole family.Methods:A 24-year-old patient with anemia for 20 years and recurrent fever for 1 month was admitted to the hematology ward of our hospital on September 7,2020.The family history information and blood samples were collected.The proband and his family members were examined for blood routine and whole-exome sequencing.The mutation of pathogenic gene was screened and verified by Sanger sequencing.The structure of the mutated protein was predicted.Relevant papers were reviewed and the process of diagnosis and treatment of CSA was reorganized and optimized to establish a long-term treatment and management plan for this patient and his whole family.Results:The whole-exome sequencing of the proband and his parents showed that the mother carried the NDUFB11 heterozygous mutation,the father did not carry the mutation,and the patient also carried the mutation.Sequencing revealed that in the CDs coding region of exon 3 of band 23 in short arm 11 of X chromosome,the cytosine at position 388 mutated into thymine（NM₀19056:exon3:c.C388T:p.R130C）,resulting in the change of arginine to cysteine in the protein sequence.This is a missense mutation and was not been reported before.Its occurrence made no significant difference according to the protein structure prediction,and its pathogenic mechanism may be related to the impaired stability of the molecule,which is not yet discovered.Sanger sequencing of all 5 members of the family showed that the proband’s mother carried the heterozygous mutation,one of his twin brothers along with himself carried the gene mutation,while his father and the other twin brother did not carry that mutation.Conclusion:NDUFB11（NM₀19056:exon3:c.C388T:p.R130C）was confirmed as the pathogenic mutation of CSA in this family.Based on the clinical phenotype analysis,the twins were also potential CSA patients,but they did not have same genotypes and that did not match with their clinical manifestations.This difference was probably caused by a certain degree of blood chimerism existing between the two brothers.