Diagnostic challenge of Diamond-Blackfan anemia in mothers and children by whole-exome sequencing

Int J Hematol. 2017 Apr;105(4):515-520. doi: 10.1007/s12185-016-2151-7. Epub 2016 Nov 23.

Abstract

Diamond-Blackfan anemia (DBA) is a pure red cell aplasia that arises from defective ribosomal proteins (RPs). Patients with this rare ribosomopathy present with neonatal anemia and occasional dysmorphism. Clinical heterogeneity and clusters of causative RP genes hamper the diagnosis and perinatal management. We report three mother-and-child pairs of anemia who were finally diagnosed by whole-exome sequencing. Each pair showed distinct disease severity and response to anemia treatment. Only one mother had the diagnostic dysmorphism, including short stature, webbed neck, and thenar hypoplasia. This mother had a frame-shift mutation of RPL11 (exon 3, c.58_59del). Her infant showed transient neonatal anemia, but had no mutations of RP genes. The other mother-child pairs had a missense mutation of RPS19 (exon 4, c.185G>A), and a splicing error of RPS7 (exon 3, c.76-1G>T), respectively. Other than the reported mutations, there were no variants in genes significantly associated with anemia. Our results suggested that whole-exome sequencing (WES) is effective for achieving a prompt and correct diagnosis of human ribosomopathy.

Keywords: Diamond–Blackfan anemia; Inherited bone marrow failure syndrome; Ribosomal protein; Whole-exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics
  • Adult
  • Anemia, Diamond-Blackfan / diagnosis*
  • Anemia, Diamond-Blackfan / genetics
  • Child, Preschool
  • Exome / genetics*
  • Facies
  • Family
  • Female
  • Humans
  • Male
  • Muscular Atrophy / genetics
  • Pedigree
  • Ribosomal Proteins / genetics
  • Sequence Analysis, DNA

Substances

  • Ribosomal Proteins
  • ribosomal protein L11
  • ribosomal protein S19
  • ribosomal protein S7

Supplementary concepts

  • Thakker Donnai syndrome