title: Brachymesomelic dysplasia with Peters anomaly of the eye results from disruptions of the X chromosome near the SHOX and SOX3 genes.
abstract: We report on a mother and son affected with an unusual skeletal dysplasia and anterior segment eye abnormalities. Their skeletal phenotype overlaps with the SHOX-related skeletal dysplasias and is intermediate between Leri-Weill dyschondrosteosis (LWD) and Langer Mesomelic dysplasia (LMD). The mother has bilateral Peters anomaly of the eye and was reported as having a new syndrome; the son had severe bilateral sclerocornea. Chromosome analysis showed that the mother has a pericentric inversion of the X chromosome [46,X,inv(X)(p22.3q27)] and the son, a resultant recombinant X chromosome [46,Y,rec(X)dup(Xq)inv(X)(p22.3q27)]. The observed skeletal and ophthalmologic abnormalities in both patients were similar in severity. The additional features of developmental delay, growth retardation, agenesis of the corpus callosum, cryptorchidism and hypoplastic scrotum in the son are consistent with Xq28 duplication. Analysis of the son's recombinant X chromosome showed that the Xp22.33 breakpoint lies 30-68 kb 5' of the SHOX gene. This finding suggests that the skeletal dysplasia in both mother and son is allelic with LWD and LMD and results from a novel misexpression of SHOX. Analysis of the Xq27.1 breakpoint localized it to a 90 kb interval 3' of the SOX3 gene, supporting a novel role of SOX3 misexpression in the development of Peters anomaly of the eye.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84132. steven.bleyl@hsc.utah.edu
authors.forename: Steven B
authors.initials: SB
authors.lastname: Bleyl
authors.forename: Janice L B
authors.initials: JL
authors.lastname: Byrne
authors.forename: Sarah T
authors.initials: ST
authors.lastname: South
authors.forename: David C
authors.initials: DC
authors.lastname: Dries
authors.forename: David A
authors.initials: DA
authors.lastname: Stevenson
authors.forename: Alan F
authors.initials: AF
authors.lastname: Rope
authors.forename: Angela M
authors.initials: AM
authors.lastname: Vianna-Morgante
authors.forename: Gary C
authors.initials: GC
authors.lastname: Schoenwolf
authors.forename: Jane D
authors.initials: JD
authors.lastname: Kivlin
authors.forename: Arthur
authors.initials: A
authors.lastname: Brothman
authors.forename: John C
authors.initials: JC
authors.lastname: Carey
mesh_terms: D000328:Adult; D001483:Base Sequence; D002871:Chromosome Banding; D041321:Chromosomes, Human, X; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D006609:High Mobility Group Proteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009693:Nucleic Acid Hybridization; D010009:Osteochondrodysplasias / Q000235:genetics*; D055748:SOXB1 Transcription Factors; D000074122:Short Stature Homeobox Protein; D014157:Transcription Factors / Q000235:genetics*; D049951:X Chromosome Inactivation
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; C106071:SHOX protein, human; C527785:SOX3 protein, human; D055748:SOXB1 Transcription Factors; D000074122:Short Stature Homeobox Protein; D014157:Transcription Factors