title: Replication of the recessive STBMS1 locus but with dominant inheritance.
abstract: OBJECTIVE
  Strabismus is a common eye disorder with a prevalence of 1% to 4%. Comitant strabismus accounts for approximately 75% of all strabismus, yet more is known about the less common incomitant disorders. Comitant strabismus is at least partly inherited, but only one recessive genetic susceptibility locus, on chromosome 7p, has been identified in one family. The purpose of this study was to determine the frequency of STBMS1 as a cause of primary nonsyndromic comitant esotropia (PNCE).
  
  
  METHODS
  Twelve families were recruited within the UK Hospital Eye Service as children attended for treatment of PNCE. All consenting persons were clinically assessed, and DNA was sampled. Chromosome 7 microsatellite markers were genotyped in all 12 families, and LOD scores were calculated under recessive and dominant models.
  
  
  RESULTS
  One family was linked to STBMS1; in three, linkage was significantly excluded; and the remainder were uninformative. Twenty-six members from three generations of the linked family were analyzed further. Five family members were defined as affected; two had esotropia with an accommodative element; and three underwent strabismus surgery and appeared to have had an infantile/early-onset esotropia. A maximum LOD score of 3.21 was obtained under a dominant mode of inheritance; a recessive model gave an LOD score of 1.2.
  
  
  CONCLUSIONS
  This study confirms that PNCE can result from sequence variants in an unknown gene at the STBMS1 locus. However, this locus accounts for only a proportion of cases, and other genetic loci remain to be identified. In contrast with the previously reported family, the pedigree described in this study is consistent with dominant rather than recessive inheritance at the STBMS1 locus.
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom. a.rice@leeds.ac.uk
authors.forename: Aine
authors.initials: A
authors.lastname: Rice
authors.forename: Jérémie
authors.initials: J
authors.lastname: Nsengimana
authors.forename: Ian G
authors.initials: IG
authors.lastname: Simmons
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
authors.forename: Janice
authors.initials: J
authors.lastname: Hoole
authors.forename: Colin E
authors.initials: CE
authors.lastname: Willoughby
authors.forename: Frances
authors.initials: F
authors.lastname: Cassidy
authors.forename: Grange A
authors.initials: GA
authors.lastname: Williams
authors.forename: Nick D
authors.initials: ND
authors.lastname: George
authors.forename: Eamonn
authors.initials: E
authors.lastname: Sheridan
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: Tim I
authors.initials: TI
authors.lastname: Hunter
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Barrett
authors.forename: David B
authors.initials: DB
authors.lastname: Elliott
authors.forename: D Tim
authors.initials: DT
authors.lastname: Bishop
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
mesh_terms: D002648:Child; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004948:Esotropia / Q000235:genetics* / Q000601:surgery; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009801:Oculomotor Muscles / Q000601:surgery; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA