Two siblings with a novel nonsense variant provide further delineation of the spectrum of recessive KLHL7 diseases

Eur J Med Genet. 2019 Sep;62(9):103551. doi: 10.1016/j.ejmg.2018.10.003. Epub 2018 Oct 6.

Abstract

Mutations in Kelch-like family member 7 (KLHL7) have recently been described as a cause of a constellation of clinical findings with descriptions of both a Crisponi syndrome (CS)/cold-induced sweating syndrome type 1 (CISS1)-like, as well as a Bohring-Opitz syndrome (BOS)-like presentation. Here we report two siblings of Guatelmalan descent with a novel homozygous nonsense mutation (p.Arg326*) in KLHL7. These children have multiple dysmorphic features and developmental delay. Interestingly, their clinical traits inconsistently overlap both the CS/CISS1-like and BOS-like phenotypes, and the siblings also have subtle differences from each other, suggesting that clinicians need to be aware of the degree of variability in the presentations of these patients. Still, there is enough in common between patients with recessive KLHL7 mutations to define a novel multisystem disease that features various neurodevelopmental, musculoskeletal, dysmorphic, and other unique components. This report adds to the clinical features and disease-associated variants of the newly-recognized spectrum of KLHL7 mutations, and offers a new description, PERCHING, for the resulting syndrome.

Keywords: Bohring-opitz syndrome; Crisponi syndrome; KLHL7; Kelch-like family member 7; PERCHING.

Publication types

  • Case Reports

MeSH terms

  • Autoantigens / genetics*
  • Child, Preschool
  • Codon, Nonsense*
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Female
  • Genes, Recessive
  • Humans
  • Infant
  • Male
  • Phenotype*
  • Siblings
  • Syndrome

Substances

  • Autoantigens
  • Codon, Nonsense
  • KLHL7 protein, human