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J Med Genet 41:e129 doi:10.1136/jmg.2004.022434
  • Online mutation report

Mutation in PITX2 is associated with ring dermoid of the cornea

  1. K Xia1,
  2. L Wu1,
  3. X Liu1,
  4. X Xi2,
  5. D Liang1,
  6. D Zheng1,
  7. F Cai1,
  8. Q Pan1,
  9. Z Long1,
  10. H Dai1,
  11. Z Hu1,
  12. B Tang3,
  13. Z Zhang1,
  14. J Xia1
  1. 1National Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan, China
  2. 2Xiangya 2nd Hospital, Central South University
  3. 3Xiangya Hospital, Central South University
  1. Correspondence to:
 Dr K Xia
 National Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan, China; nlmglcyxysm.net

    Ring dermoid of the cornea (RDC, MIM180550) is an autosomal dominantly inherited syndrome characterised by bilateral annular limbal dermoids with corneal and conjunctival extension. The genetic basis of RDC is unknown. We report linkage of chromosome 4q24-q26 to RDC and identification of a missense mutation in PITX2 in 17 disease affected individuals but not in eight genetically related normal individuals in a large Chinese family.

    METHODS

    A large Chinese family with 17 individuals affected by the RDC was identified (figs 1 and 2). All patients were diagnosed by the same physician (XHX). Informed written consent for blood sample collection was obtained from all participants.

    Figure 1

     Eyes affected by ring dermoid of the cornea (RDC) in two patients, II-2 (upper panel) and IV-3 (lower panel). Yellow-white tumour-like apophyses are visible on the corneal border of both eyes. The apophyses are diffuse in the superficial layer of the cornea and conjunctiva. The corneal border is not clear and the diameter of the transparent region of cornea is diminished to about 7–8 mm. The upward shift of the right pupil of IV-3 is caused by cataract resection (the affected individual, IV-3, also has bilateral glaucoma and congenital cataracts in the right eye).

    Figure 2

     Recombination analysis of the family with ring dermoid of the cornea (RDC). Pedigree of the family affected by RDC and haplotype analysis for 14 markers on 4q22-q26. Markers (from top to bottom) are centromere-D4S1560-D4S2966-D4S1572-D4S1570-D4S1564-D4S2945-D4S2989-D4S1616-D4S406-D4S193-D4S1613-D4S1522-D4S1612-D4S427-telomere. The haplotype co-segregating with the disorder is boxed.

    Linkage analysis and genotyping were done essentially as previously described.1 Genome-wide screening was carried out with 382 microsatellite markers covering all autosomal chromosomes, with an average interval of 10 cM (ABI PRISM™ linkage mapping set, version 2.0). Fine …