Compound heterozygous mutations of Fanc A gene in two children with Fanconi anemia / 中华实用儿科临床杂志

ABSTRACT

The clinical features and laboratory tests results of two cases with Fanconi anemia (FA) who were admitted to the Department of Children′s Hematology and Endocrinology, the Provincial Hospital Affiliated to Shandong First Medical University in 2017 were analyzed.Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) of FA-related genes was carried out.One case was female, 4 years and 3 months old.The other case was a 6-year-old male.The main manifestations were recurrent fever, asthenia and bleeding points in both legs.The girl had milk coffee spots scattered on her legs and waist, and her left thumb nail was absent.The boy had no obvious physical examination abnormality, but his left atrium and left ventricle were large and segmental myocardial damage could be seen by echocardiography.Bone marrow biopsies of both cases showed hypo-proliferation (40%) or extremely low proliferation (10%), and no megakaryocyte was found.There were no significant abnormalities in chromosome aberration, single cell gel electrophoresis, cluster of differentiation(CD) 41, CD 55, and CD 59 and chromosome karyotype.Gene sequencing revealed that the two children had compound heterozygous mutations of Fanc A gene, which came from parents.The heterozygous mutation of c1838delT was found in the exon 21 of the female child and her father, which resulted in amino acid shift mutation pIi613Tfs*27.The heterozygous deletion mutations in exons 1-3 of Fanc A gene were found in the female child and her mother by the MLPA results.The gene sequencing analysis of the male child and his family members showed the heterozygous mutation of c4124_4125del in the exon 41 of the child and his mother, which resulted in amino acid shift mutation p. T1375Sfs*49.The heterozygous deletion mutations were observed in exons 23-40 of the male child and his father, according to the MLPA results.The main basis of diagnosis of FA is to sequence the related genes of suspected children.The c1838delT is a new mutation of Fanc A gene.