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This abstract is assigned to session SBO-BOG Free papers: Genetica/Génétique

Title

Genotype-phenotype correlation of Stickler syndrome caused by mutations in the COL2A1 gene

Purpose	To investigate and correlate the allelic heterogeneity and phenotypic variability in Stickler syndrome patients with a COL2A1 mutation
Methods	In 188 probands with the referring diagnosis of Stickler syndrome, the 54 exons and intronic boundaries of COL2A1 were amplified by PCR and analysed by either a mutation scanning technique or bidirectional fluorescent DNA sequencing. The effect of splice site alterations was investigated by analysing RNA
Results	We identified 100 heterozygous COL2A1 mutations, including 1 entire gene deletion, 27 nonsense mutations, 35 frameshift mutations, 25 splice site alterations, 1 synonymous mutation altering splicing, 5 arginine-to-cysteine substitutions and 5 glycine alterations. Each of the 13 investigated splice site mutations was shown to result in a premature stop codon. A binary logistic regression analysis of the clinical features, revealed 7 major indicators for a type 2 collagenopathy in Stickler syndrome: vitreous abnormalities, retinal detachment, retinal abnormalities, low nasal bridge, cleft palate, micrognathia and positive family history
Conclusion	Stickler syndrome type 1 is predominantly caused by loss-of-function mutations in the COL2A1 gene. We developed a phenotypic scoring system that facilitates distinction between patients with and without a COL2A1 mutation

Author 1

Last name	HOORNAERT
Initials	KP
Department	Dept of Ophth and Ctr for Med Genet, Ghent Univ Hosp
City	Ghent, Belgium

Author 2

Last name	Dewinter
Initials	C
Department	Ctr for Med Genet, Ghent Univ Hosp
City	Ghent, Belgium

Author 3

Last name	Vereecke
Initials	I
Department	Ctr for Med Genet, Ghent Univ Hosp
City	Ghent, Belgium

Author 4

Last name	Van Aken
Initials	EH
Department	Dept of Ophth, Ghent Univ Hosp, Ghent, Belgium
City	Ghent, Belgium

Author 5

Last name	Leroy
Initials	BP
Department	Dept of Ophth and Ctr for Med Genet, Ghent Univ Hosp, Ghent, Belgium
City	Ghent, Belgium

Author 6

Last name	Coucke
Initials	PJ
Department	Ctr for Med Genet, Ghent Univ Hosp
City	Ghent, Belgium

Author 7

Last name	Mortier
Initials	GR
Department	Ctr for Med Genet, Ghent Univ Hosp
City	Ghent, Belgium