advertisement
Abstract #25410 Published in IGR 12-1
LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma
Desir J; Sznajer Y; Depasse F; Roulez F; Schrooyen M; Meire F; Abramowicz MEuropean Journal of Human Genetics 2010;
The latent TGF(beta)-binding proteins (LTBPs) and fibrillins are a superfamily of large, multidomain proteins with structural and TGF(beta)-signalling roles in the extracellular matrix. Their importance is underscored by fibrillin-1 mutations responsible for Marfan syndrome, but their respective roles are still incompletely understood. We report here on two families where children from healthy, consanguineous parents, presented with megalocornea and impaired vision associated with small, round, dislocated lenses (microspherophakia and ectopia lentis) and myopia, as well as a high-arched palate, and, in older children, tall stature with an abnormally large arm span over body height ratio, that is, associated features of Marfan syndrome. Glaucoma was not present at birth, but was diagnosed in older children. Whole genome homozygosity mapping followed by candidate gene analysis identified homozygous truncating mutations of LTBP2 gene in patients from both families. Fibroblast mRNA analysis was consistent with nonsense-mediated mRNA decay, with no evidence of mutated exon skipping. We conclude that biallelic null LTBP2 mutations cause the ocular phenotype in both families and could lead to Marfan-like features in older children. We suggest that intraocular pressures should be followed-up in young children with an ocular phenotype consisting of megalocornea, spherophakia and/or lens dislocation, and recommend LTBP2 gene analysis in these patients.European Journal of Human Genetics advance online publication, 24 February 2010; doi: 10.1038/ejhg.2010.11.
IRIBHM, Universite Libre de Bruxelles (ULB), Brussels, Belgium
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
9.4.2 Glaucomas associated with disorders of the cornea, conjunctiva, sclera (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)
9.4.15 Glaucoma in relation to systemic disease (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)
