Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a Chinese girl with Fanconi Anemia

Eur J Med Genet. 2017 Jul;60(7):369-373. doi: 10.1016/j.ejmg.2017.04.008. Epub 2017 Apr 15.

Abstract

Fanconi Anemia (FA) is a rare genetically heterogeneous disorder with 17 known complement groups caused by mutations in different genes. FA complementation group L (FA-L, OMIM #608111) occurred in 0.2% of all FA and only eight mutant variants in the FANCL gene were documented. Phenotype and genotype correlation in FANCL associated FA is still obscure. Here we describe a Chinese girl with FA-L caused by a novel homozygous mutation c.822_823insCTTTCAGG (p.Asp275LeufsX13) in the FANCL gene. The patient's clinical course was typical for FA with progression to bone marrow failure, and death from acute myelomonocytic leukemia (AML-M4) at 9 years of age. Mutation analysis also detected a likely somatic c.2608G > A (p.Gly870Ser) in the SETBP1 gene. Consistent copy number losses of 7q and 18p and gains of 3q and 21q and accumulated non-clonal single cell chromosomal abnormalities were detected in blood leukocytes as her FA progressed. This is the first Chinese FA-L case caused by a novel FANCL mutation. The somatic gene mutation and copy number aberrations could be used to monitor disease progression and the clinical findings provide further information for genotype-phenotype correlation for FA-L.

Keywords: FANCL gene; Fanconi Anemia; SETBP1 gene.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Biomarkers / blood
  • Carrier Proteins / genetics*
  • Child, Preschool
  • Chromosome Aberrations
  • DNA Copy Number Variations
  • Fanconi Anemia / blood
  • Fanconi Anemia / diagnosis
  • Fanconi Anemia / genetics*
  • Fanconi Anemia Complementation Group L Protein / genetics*
  • Female
  • Heterozygote
  • Homozygote
  • Humans
  • Nuclear Proteins / genetics*

Substances

  • Biomarkers
  • Carrier Proteins
  • Nuclear Proteins
  • SETBP1 protein, human
  • FANCL protein, human
  • Fanconi Anemia Complementation Group L Protein