Donnai-Barrow syndrome (DBS/FOAR) in a child with a homozygous LRP2 mutation due to complete chromosome 2 paternal isodisomy

Am J Med Genet A. 2008 Jul 15;146A(14):1842-7. doi: 10.1002/ajmg.a.32381.

Abstract

Donnai-Barrow syndrome [Faciooculoacousticorenal (FOAR) syndrome; DBS/FOAR] is a rare autosomal recessive disorder resulting from mutations in the LRP2 gene located on chromosome 2q31.1. We report a unique DBS/FOAR patient homozygous for a 4-bp LRP2 deletion secondary to paternal uniparental isodisomy for chromosome 2. The propositus inherited the mutation from his heterozygous carrier father, whereas the mother carried only wild-type LRP2 alleles. This is the first case of DBS/FOAR resulting from uniparental disomy (UPD) and the fourth published case of any paternal UPD 2 ascertained through unmasking of an autosomal recessive disorder. The absence of clinical symptoms above and beyond the classical phenotype in this and the other disorders suggests that paternal chromosome 2 is unlikely to contain imprinted genes notably affecting either growth or development. This report highlights the importance of parental genotyping in order to give accurate genetic counseling for autosomal recessive disorders.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adult
  • Agenesis of Corpus Callosum
  • Base Sequence
  • Child
  • Chromosomes, Human, Pair 2 / genetics*
  • DNA / genetics
  • Encephalocele / genetics
  • Female
  • Hearing Loss, Sensorineural / genetics
  • Hernia, Inguinal / congenital
  • Hernia, Inguinal / genetics
  • Homozygote
  • Humans
  • Hypertelorism / genetics
  • Low Density Lipoprotein Receptor-Related Protein-2 / genetics*
  • Male
  • Mutation
  • Myopia / genetics
  • Pedigree
  • Proteinuria / genetics
  • Sequence Deletion
  • Syndrome
  • Uniparental Disomy / genetics*

Substances

  • Low Density Lipoprotein Receptor-Related Protein-2
  • DNA