Novel compound heterozygous variants in NHLRC2 in a patient with FINCA syndrome

J Hum Genet. 2020 Oct;65(10):911-915. doi: 10.1038/s10038-020-0776-0. Epub 2020 May 21.


Two variants in the ubiquitously expressed NHLRC2 gene have been reported to cause a lethal fibrotic cerebropulmonary disease termed fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome in three Finnish children. Our objective was to determine the genetic basis of disease in a new patient with clinical features of FINCA syndrome using whole-exome sequencing (WES) and confirmation by Sanger sequencing. The patient has one known and one novel variant in NHLRC2 (c.442T>G, p.D148Y and c.428C>A, p.H143P, respectively). p.H143P is extremely rare and is not present in the gnomAD database of >140,000 allele sequences from healthy humans. Both variants affect the highly conserved N-terminal thioredoxin (Trx)-like domain of NHLRC2 and are predicted to be damaging. We conclude that a compound heterozygous combination of a known and a novel variant in NHLRC2 causes FINCA syndrome in a 2-year-old Ukrainian patient, underscoring the importance of NHLRC2 as a central regulator of fibrosis.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Angiomatosis / genetics*
  • Brain Neoplasms / genetics*
  • Cardiomegaly / genetics*
  • Cardiomegaly / pathology
  • Child, Preschool
  • Exome Sequencing
  • Fibrosis
  • Heterozygote
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Lung Diseases / genetics*
  • Male
  • Models, Molecular
  • Neurodegenerative Diseases / genetics*
  • Pedigree
  • Point Mutation*
  • Protein Conformation
  • Protein Domains
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Syndrome


  • Intracellular Signaling Peptides and Proteins
  • NHLRC2 protein, human