P-48: LTBP2 Mutation in Autosomal Recessive Weill-Marchesani Syndrome (Pages: 61-62)

Jelodari-Mamaghani S *, Haji-Seyed-Javadi R , Shahin Yazdani N , Elahi E ,


Objective: Weill-Marchesani syndrome(WMS) is a rare connective tissue disorder characterized by short stature; brachydactyly; joint stiffness; eye anomalies, including ectopia lentis, microspherophakia, severe myopia, and glaucoma. Despite the disease’s clinical homogeneity, autosomal recessive and autosomal dominant modes of inheritance have been reported. FBN1 is a causative gene in the dominant form of the disease. In a large family with dominant WMS, an in-frame (24 bp) deletion in FBN1, which is implicated in Marfan syndrome was identified. In case of recessive WMS ADAMTS10 and ADAMTS17 genes were examined and different mutations were reported. Another study showed that in an isolated form of microspherophakia, one of the features of WMS, LTBP2 gene was mutated. All proteins which are coded by these genes found in extra cellular matrix. ADAMTS is a family of extracellular proteases found in both mammals and invertebrates. FBN1 is a major microfibrillar component of the extracellular matrix (ECM). Latent TGFβ Binding protein -2 (LTBP2) is also a microfibrillar component of the extracellular matrix with high structural similarity to Fibrillin. LTBP2 was identified as a primary congenital glaucoma (PCG) causing gene. Several PCG patients harboring LTBP2 mutations were observed to be also affected with ectopia lentis, which is a characteristic of WMS patients. The association of LTBP2 with Fibrillin in the extracellular matrix, and the observation of EL in some PCG patients harboring LTBP2 mutations prompted a further investigation of possible role of LTBP2 in promoting WMS. Materials and Methods: We therefore screened all 36 exons of LTBP2 in 4 WMS families with autosomal recessive inheritence, all of whom exhibited lens displacement. In addition to several known polymorphisms, we found a homozygous mutation in exon 24 of 2 siblings of a family. Results: We will examine other members of this family to confirm the effect of this mutation on the disease. Conclusion: According to the relationship between fibrilin1 and LTBP2 protein in the extra cellular matrix there could be a possible role for LTBP2 gene in WMS patients