title: A new recessively inherited disorder composed of foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis maps to chromosome 16q23.3-24.1.
abstract: OBJECTIVE
  We have previously described two families with unique phenotypes involving foveal hypoplasia. The first family (F1) presented with foveal hypoplasia and anterior segment dysgenesis, and the second family (F2) presented with foveal hypoplasia and chiasmal misrouting in the absence of albinism. A genome-wide linkage search in family F1 identified a 6.5 Mb locus for this disorder on chromosome 16q23.2-24.1. The aim of this study was to determine if both families have the same disorder and to see if family F2 is also linked to the 16q locus.
  
  
  METHODS
  Family members underwent routine clinical examination. Linkage was determined by genotyping microsatellite makers and calculating logarithm of the odds (LOD) scores. Locus refinement was undertaken with single nucleotide polymorphism (SNP) microarray analysis.
  
  
  RESULTS
  The identification of chiasmal misrouting in family F1 and anterior segment abnormalities in family F2 suggested that the families have the same clinical phenotype. This was confirmed when linkage analysis showed that family F2 also mapped to the 16q locus. The single nucleotide polymorphism microarray analysis excluded a shared founder haplotype between the families and refined the locus to 3.1 Mb.
  
  
  CONCLUSIONS
  We report a new recessively inherited syndrome consisting of foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis, which we have abbreviated to FHONDA syndrome. The gene mutated in this disorder lies within a 3.1 Mb interval containing 33 genes on chromosome 16q23.3-24.1 (chr16:83639061 - 86716445, hg19).
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institutes of Molecular Medicine, University of Leeds, Leeds, UK.
authors.forename: Musallam
authors.initials: M
authors.lastname: Al-Araimi
authors.forename: Bishwanath
authors.initials: B
authors.lastname: Pal
authors.forename: James A
authors.initials: JA
authors.lastname: Poulter
authors.forename: Maria M
authors.initials: MM
authors.lastname: van Genderen
authors.forename: Ian
authors.initials: I
authors.lastname: Carr
authors.forename: Tomas
authors.initials: T
authors.lastname: Cudrnak
authors.forename: Lawrence
authors.initials: L
authors.lastname: Brown
authors.forename: Eamonn
authors.initials: E
authors.lastname: Sheridan
authors.forename: Moin D
authors.initials: MD
authors.lastname: Mohamed
authors.forename: John
authors.initials: J
authors.lastname: Bradbury
authors.forename: Manir
authors.initials: M
authors.lastname: Ali
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
mesh_terms: D000293:Adolescent; D000869:Anterior Eye Segment / Q000002:abnormalities* / Q000473:pathology; D002648:Child; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005190:Family; D005260:Female; D005584:Fovea Centralis / Q000002:abnormalities* / Q000473:pathology; D005808:Genes, Recessive / Q000235:genetics*; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D009897:Optic Chiasm / Q000002:abnormalities* / Q000473:pathology; D009900:Optic Nerve / Q000002:abnormalities*; D010375:Pedigree