Replication of the recessive STBMS1 locus but with dominant inheritance.

PubMed ID: 19218600

Author(s): Rice A, Nsengimana J, Simmons IG, Toomes C, Hoole J, Willoughby CE, Cassidy F, Williams GA, George ND, Sheridan E, Young TL, Hunter TI, Barrett BT, Elliott DB, Bishop DT, Inglehearn CF. Replication of the recessive STBMS1 locus but with dominant inheritance. Invest Ophthalmol Vis Sci. 2009 Jul;50(7):3210-7. doi: 10.1167/iovs.07-1631. Epub 2009 Feb 14. PMID 19218600

Journal: Investigative Ophthalmology & Visual Science, Volume 50, Issue 7, Jul 2009

PURPOSE 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.