Case report: a novel KERA mutation associated with cornea plana and its predicted effect on protein function

BMC Medical Genetics

Zeynep Tümer²  Karen Grønskov²  Hanne Jensen⁴  Anette Bygum¹  Pernille Harris³  Birgitte Bertelsen²  Laura Roos² 

[1] Department of Dermatology, Odense University Hospital, Odense, Denmark;Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Gl. Landevej 7, Glostrup 2600, Denmark;Department of Chemistry, Technical University of Denmark, Kemitorvet Build. 207, Kgs. Lyngby, DK-2800, Denmark;Eye Clinic, Department of Ophthalmology, Copenhagen University Hospital, Glostrup, Denmark

关键词: Leucin rich repeat domain;    Protein modelling;    Missense mutation;    KERA protein;    Hypotrichosis;    Cornea plana 2;   

Others  :  1220382
DOI  :  10.1186/s12881-015-0179-9

 received in 2014-07-26, accepted in 2015-05-15,  发布年份 2015

【 摘 要 】

Background

Cornea plana (CNA) is a hereditary congenital abnormality of the cornea characterized by reduced corneal curvature, extreme hypermetropia, corneal clouding and hazy corneal limbus. The recessive form, CNA2, is associated with homozygous or compound heterozygous mutations of the keratocan gene (KERA) on chromosome 12q22. To date, only nine different disease-associated KERA mutations, including four missense mutations, have been described.

Case presentation

In this report, we present clinical data from a Turkish family with autosomal recessive cornea plana. In some of the affected individuals, hypotrichosis was found. KERA was screened for mutations using Sanger sequencing. We detected a novel KERA variant, p.(Ile225Thr), that segregates with the disease in the homozygous form. The three-dimensional structure of keratocan protein was modelled, and we showed that this missense variation is predicted to destabilize the structure of keratocan, leading to the classical ocular phenotype in the affected individuals. All the four known missense mutations, including the variation found in this family, affect the conserved residues of the leucine rich repeat domain of keratocan. These mutations are predicted to result in destabilization of the protein.

Conclusion

We present the 10th pathogenic KERA mutation identified so far. Protein modelling is a useful tool in predicting the effect of missense mutations. This case underline the importance of the leucin rich repeat domain for the protein function, and this knowledge will ease the interpretation of future findings of mutations in these areas in other families with cornea plana.

【 授权许可】

   
2015 Roos et al.

【 图 表 】

Fig. 1.

Fig. 2.

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