Stickler syndrome without eye involvement is caused by mutations in COL11A2, the gene encoding the α2(XI) chain of type XI collagen☆,☆☆,★,★★
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Clinical Description and Research Method
The proband was born with RS and also has moderate sensorineural hearing loss, midfacial flattening, a depressed nasal bridge, and a small nose with upturned tip. Her height is at the 10th percentile for age and the remainder of her physical examination is normal. Eight additional family members have similar features and are considered to be affected (Fig. 2). All have malar flattening, depression of the nasal bridge, and anteversion of the nares; these features persist in the affected adults (
RESULTS
Single strand conformational polymorphisms were detected in two overlapping reverse trancriptase polymerase chain reaction amplified products. These products were sequenced and double sequence suggesting heterozygosity for a 27 basepair deletion involving nucleotides 2775-2801 (based on the COL11A2 transcription start site5) was found. The deletion is predicted to occur within exon 39 of the COL11A2 gene.8 To confirm that this deletion is present at the genomic level we amplified exon 39 from
DISCUSSION
We have identified a COL11A2 mutation in a family with features of SS who lack eye involvement. Similar mutations in other fibrillar collagens cause dominant negative effects on collagen synthesis, secretion, or function.4 Therefore it is likely that a dominant negative effect will also result from this mutation. Our result confirms that the COL11A2 gene product, α2(XI), has a less important role in the eye than in other tissues where collagen XI is expressed.5
COL11A2 mutations have previously
Acknowledgements
We thank Drs. T. Wilcox, H. Brunner, and M. Vikkula for sharing clinical and research expertise; Ms. L. Kerr for performing the EBV transformation of lymphocytes; and the family for participating in this study.
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From the Departments of Genetics and Ophthalmology, Case Western Reserve University School of Medicine and the Center for Human Genetics, University Hospitals of Cleveland.
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This work was supported by a Case Western Reserve University School of Medicine Research Initiation Grant, NIH grant AR-43827, and an Arthritis Investigator Award from the Arthritis Foundation.
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Reprint requests: Matthew L. Warman, MD, Genetics, BRB-719, 2109 Adelbert Rd., Cleveland, OH 44106.
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