[1962] Ultrastructural Features of Gelophyisic Dysplasia: Role of Electron Microscopy in Diagnosis

J Hicks, JP Barrish, SH Zhu, N Brunetti-Pierri. Texas Children's Hospital & Baylor College of Medicine, Houston, TX; Baylor College of Medicine, Houston, TX

Background: Geleophysic Dysplasia (GD), an autosomal recessive disorder, is a member of the Acromelic Dysplasia Group, which includes Weill-Marchesani Syndrome and Acromicric Dysplasia. All 3 disorders are characterized by short stature, short hands, stiff joints, delayed bone age, cone-shaped epiphyses, thick skin and heart disease. Molecular testing is in the development phase and of considerable expense. GD is a lysosomal storage disease that may be identified by electron microscopy of cultured fibroblasts.
Design: 8 children with clinically suspected GD underwent skin punch biopsies to establish fibroblast cultures for electron microscopic examination, and for future genetic and molecular testing. The study population consisted of 5 males and 3 females with an age range from 13 months to 13 years. Fibroblasts were harvested from the cell cultures, and prepared for electron microscopic examination. 4 skin cell cultures of normal fibroblasts were examined as controls.
Results: Light microscopic examination of the semi-thin sections of the cultured normal and GD fibroblasts showed cellular specimens. The fibroblasts were round to ovoid in outline and had a moderate amount of cytoplasm. The nuclei tended to have indented surfaces and were somewhat irregular in outline. There was adequate preservation for electron microscopic examination. Both normal and GD fibroblasts showed a mild to moderate degree of rough endoplasmic reticulum dilation with granular material present. The normal fibroblasts had typical cell organelles. GD fibroblasts possessed frequent lysosomal storage vacuoles. These lysosomes contained lamellar structures which vaguely resembled myelin-like figures, which are characteristic for GD. Such structures were absent in all normal fibroblasts.
Conclusions: ADAMTSL2 gene and 6 other genes within a critical interval on chromosome 9q34.2-q34.3 have been linked to Geleophysic Dysplasia. ADAMSTL2 is involved in microfibrillar networks, and mutations lead to reduced secretion of the proteins and misfolding of mutated ADAMTSL2 proteins. ADAMTSL2 interacts with latent TGF-beta-binding protein-1 nuclear localization of phosphorylated SMAD2, a regulator of cell growth and apoptosis. Electron microscopic detection of lysosomes containing lamellar structures in GD fibroblasts, most likely represents mutated ADAMTSL2 protein and an attempt to degrade the mutated protein. Electron microscopy plays a crucial role in GD diagnosis.
Category: Ultrastructural

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 260, Wednesday Morning


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