Article

Clinical variability of Stickler syndrome with a COL2A1 haploinsufficiency mutation: Implications for genetic counselling

University of Zurich, Zürich, Zurich, Switzerland
Journal of Medical Genetics (Impact Factor: 6.34). 05/2000; 37(4):318-20. DOI: 10.1136/jmg.37.4.318
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Available from: Beat Steinmann, Dec 19, 2013
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    • "Medical professionals believe that one in 10,000 persons may be affected by stickler syndrome. Many researchers have reported clinical (Faber et al., 2000; and Rose et al., 2005) and genetic (Snead and Yates, 1999) studies on stickler syndrome. Characterization (Cheah et al., 1985) of collagen type II gene and structural studies (Yoshioka and Ramirez, 1990; and Vuoristo et al., 1995) on type XI genes were also reported. "

    Full-text · Dataset · Sep 2014
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    • "Medical professionals believe that one in 10,000 persons may be affected by stickler syndrome. Many researchers have reported clinical (Faber et al., 2000; and Rose et al., 2005) and genetic (Snead and Yates, 1999) studies on stickler syndrome. Characterization (Cheah et al., 1985) of collagen type II gene and structural studies (Yoshioka and Ramirez, 1990; and Vuoristo et al., 1995) on type XI genes were also reported. "
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    ABSTRACT: Collagen is the most abundant protein in the human body. Collagen forms a major part of connective tissue, which can be described as the supportive tissue of the organs of the body. Defect in collagen causes various syndromes, including stickler syndrome. Here, stickler syndrome associated 11 human collagen proteins retrieved from National Center for Biotechnology Information (NCBI) Entrez protein database are characterized by using proteomics tools and online proteomics servers to give a detailed description of stickler syndrome-causing human collagen proteins. Primary structure analysis shows that all the 11 stickler syndrome-causing collagen proteins are rich in glycine (23-28%) and proline (16-18%) residues. The computed pI value indicates that the collagen proteins, NP_542197.1, NP_542196.1, NP_001845.2, NP_542411.1, AAF04726.1, AAF04725.1 and AAF04724.1, are acidic, (pI 7), and the protein, NP_001835.2 is neutral (pI =~ 7) in character. The very low Aliphatic Index (AI) (38-50) infers that the collagen proteins may become unstable at high temperature. Based on the Instability Index, the Expasy’s ProtParam classifies the collagen proteins as stable. Secondary structure analysis shows that all the 11 collagen proteins are found to be of predominant coil structure content (100%), and the Secondary Structure Content Prediction server (SSCP) classifies as irregular secondary structure class. The irregular structure of collagen proteins is due to the rich content of more flexible glycine and hydrophobic proline amino acids. SOSUI server predicts one transmembrane region (IRLGAPQSLVLLTLLVAAVLRCQ) in alpha 1 type II collagen proteins. The predicted transmembrane region is visualized and analyzed using helical wheel plot generated by EMBOSS pepwheel tool and it is found that the helical wheel consists of hydrophobic residues. The hydrophobicity of predicted transmembrane region is also well-documented by the Kyte and Doolittle mean hydrophobicity profile.
    Full-text · Article · Dec 2009
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    • "Variants of Stickler syndrome have been designated STL1 (vitreous type with mutations in COL2A1 gene), STL2 (early onset hearing loss and mutations in the COL 11A1 gene) and STL3 (non-ocular type caused by mutations in the COL11A2 gene). Numerous genetic mutations of Stickler syndrome cases are STL1 variety and are caused by mutations in the COL2A1 gene [29]. In practice, however, there are difficulties in obtaining molecular analysis because of the size, complexity and the number of gene involved and the high cost of these investigations. "
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    ABSTRACT: Stickler syndrome is among the most common autosomal dominant connective tissue disorders but is often unrecognised and therefore not diagnosed by clinicians. Despite much speculation, the cause of osteochondrosis in general and osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) in particular remain unclear. Etiological understanding is essential. We describe a pair of family subjects presented with OCD and OSS as a symptom complex rather than a diagnosis. Detailed clinical and radiographic examinations were undertaken with emphasis on the role of MRI imaging. Magnetic resonance imaging may allow early prediction of articular lesion healing potential in patients with Stickler syndrome. The phenotype of Stickler syndrome can be diverse and therefore misleading. The expectation that the full clinical criteria of any given genetic disorder such as Stickler syndrome will always be present can easily lead to an underestimation of these serious inheritable disorders. We report here two family subjects, a male proband and his aunt (paternal sister), both presented with the major features of Stickler syndrome. Tall stature with marfanoid habitus, astigmatism/congenital vitreous abnormality and submucus cleft palate/cleft uvula, and enlarged painful joints with early onset osteoarthritis. Osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) were the predominating joint abnormalities. We observed that the nature of the articular and physeal abnormalities was consistent with a localised manifestation of a more generalised epiphyseal dysplasia affecting the weight-bearing joints. In these two patients, OCD and OSS appeared to be the predominant pathologic musculoskeletal consequences of an underlying Stickler's syndrome. It is empirical to consider generalised epiphyseal dysplasia as a major underlying causation that might drastically affect the weight-bearing joints.
    Full-text · Article · Mar 2009 · Pediatric Rheumatology
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