Deletions within COL11A1 in Type 2 stickler syndrome detected by multiplex ligation-dependent probe amplification (MLPA)

BMC Medical Genetics

Allan Richards⁵  Martin Snead¹  Gregory Fincham¹  Vivienne McConnell²  Marcia Rodrigues³  Teresa Lourenco³  Alan Donaldson⁶  Abdellatif Errami⁴  Sarah Waller⁷  Raymon Vijzelaar⁴ 

[1]Vitreoretinal Service, Department of Ophthalmology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK

[2]Northern Ireland Regional Genetics Service, Belfast City Hospital, Belfast, UK

[3]Department of Medical Genetics, Hospital de Dona Estefânia, Lisbon, Portugal

[4]MRC-Holland, Amsterdam, The Netherlands

[5]Department of Pathology, University of Cambridge, Cambridge, UK

[6]Clinical Genetics, University Hospitals Bristol, NHS Trust, Bristol, UK

[7]East Anglian Regional Genetics Laboratory, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK

关键词: Stickler syndrome;    Molecular analysis;    MLPA;    COL11A1;   

Others  :  1177705
DOI  :  10.1186/1471-2350-14-48

 received in 2013-02-06, accepted in 2013-04-23,  发布年份 2013

【 摘 要 】

Background

COL11A1 is a large complex gene around 250 kb in length and consisting of 68 exons. Pathogenic mutations in the gene can result in Stickler syndrome, Marshall syndrome or Fibrochondrogenesis. Many of the mutations resulting in either Stickler or Marshall syndrome alter splice sites and result in exon skipping, which because of the exon structure of collagen genes usually leaves the message in-frame. The mutant protein then exerts a dominant negative effect as it co-assembles with other collagen gene products. To date only one large deletion of 40 kb in the COL11A1, which was detected by RT-PCR, has been characterized. However, commonly used screening protocols, utilizing genomic amplification and exon sequencing, are unlikely to detect such large deletions. Consequently the frequency of this type of mutation is unknown.

Case presentations

We have used Multiplex Ligation-Dependent Probe Amplification (MLPA) in conjunction with exon amplification and sequencing, to analyze patients with clinical features of Stickler syndrome, and have detected six novel deletions that were not found by exon sequencing alone.

Conclusion

Exon deletions appear to represent a significant proportion of type 2 Stickler syndrome. This observation was previously unknown and so diagnostic screening of COL11A1 should include assays capable of detecting both large and small deletions, in addition to exon sequencing.

【 授权许可】

   
2013 Vijzelaar et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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