Brachymesomelic dysplasia with Peters anomaly of the eye results from disruptions of the X chromosome near the SHOX and SOX3 genes

• Published in: American journal of medical genetics. Part A Vol. 143A; no. 23; pp. 2785 - 2795
• Main Authors: Bleyl, Steven B., Byrne, Janice L.B., South, Sarah T., Dries, David C., Stevenson, David A., Rope, Alan F., Vianna-Morgante, Angela M., Schoenwolf, Gary C., Kivlin, Jane D., Brothman, Arthur, Carey, John C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2007; Wiley-Liss
• Subjects: Adult; Base Sequence; Biological and medical sciences; Chromosome Banding; Chromosomes, Human, X; Diseases of the osteoarticular system; DNA Primers; DNA-Binding Proteins - genetics; dyschondrosteosis; Eye Abnormalities - genetics; Female; High Mobility Group Proteins - genetics; Homeodomain Proteins - genetics; Humans; Infant, Newborn; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Malformations of the eye; Medical genetics; Medical sciences; mesomelic dysplasia; Nucleic Acid Hybridization; Ophthalmology; Osteochondrodysplasias - genetics; Peters anomaly; sclerocornea; Short Stature Homeobox Protein; SHOX; SOX3; SOXB1 Transcription Factors; Transcription Factors - genetics; X Chromosome Inactivation; X-chromosome inversion; Chromosomal aberration; Dysplasia; Peters syndrome; Diseases of the osteoarticular system; Dyschondrosteosis; Sclerocornea; X-chromosome inversion; Congenital disease; Genetic disease; Eye; SOX3; Eye disease; mesomelic dysplasia; Gene; Malformation; Peters anomaly; SHOX; Abnormal chromosome; X-Chromosome; Disruption; Osteochondrodysplasia; Chromosome inversion
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32036

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. © 2007 Wiley‐Liss, Inc.