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Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions.
Invest Ophthalmol Vis Sci. 2002 Jun; 43(6):1843-9.IO

Abstract

PURPOSE

Mutations in the forkhead transcription factor gene FOXC1 on 6p25 cause a range of ocular developmental abnormalities, with associated glaucoma. However, FOXC1 mutations have not been found in all similarly affected pedigrees mapping to this interval. This study was undertaken to investigate the potential role of 6p25 rearrangements in causing such phenotypes.

METHODS

Two large families with autosomal dominant iris hypoplasia and early-onset glaucoma, 21 probands with Axenfeld-Rieger phenotypes not attributable to PITX2 mutations, and 7 individuals with documented 6p25 cytogenetic rearrangements, were investigated by genotyping and fluorescence in situ hybridization, with markers and probes from the 6p25 region.

RESULTS

Interstitial 6p25 duplications were present in the unrelated families with iris hypoplasia, whereas an interstitial 6p25 deletion was identified in one Axenfeld-Rieger pedigree. Larger cytogenetic rearrangements, leading to trisomy or monosomy of the 6p25 region, resulted in microcornea and Rieger syndrome phenotypes, respectively. All the rearrangements encompassed FOXC1, increasing or decreasing the number of FOXC1 copies present, and appeared to correlate with the phenotypes observed.

CONCLUSIONS

These findings represent the first example of both interstitial duplications and deletions cosegregating with a human developmental disorder that is attributable to altered dose of transcription factor. The data presented provide additional evidence for the pathogenicity of altered gene dosage of FOXC1 and suggest that a common mechanism is responsible for rearrangements of 6p25.

Authors+Show Affiliations

Department of Molecular Genetics, Institute of Ophthalmology, London, United Kingdom. ojlehmann@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12036988

Citation

Lehmann, Ordan J., et al. "Ocular Developmental Abnormalities and Glaucoma Associated With Interstitial 6p25 Duplications and Deletions." Investigative Ophthalmology & Visual Science, vol. 43, no. 6, 2002, pp. 1843-9.
Lehmann OJ, Ebenezer ND, Ekong R, et al. Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions. Invest Ophthalmol Vis Sci. 2002;43(6):1843-9.
Lehmann, O. J., Ebenezer, N. D., Ekong, R., Ocaka, L., Mungall, A. J., Fraser, S., McGill, J. I., Hitchings, R. A., Khaw, P. T., Sowden, J. C., Povey, S., Walter, M. A., Bhattacharya, S. S., & Jordan, T. (2002). Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions. Investigative Ophthalmology & Visual Science, 43(6), 1843-9.
Lehmann OJ, et al. Ocular Developmental Abnormalities and Glaucoma Associated With Interstitial 6p25 Duplications and Deletions. Invest Ophthalmol Vis Sci. 2002;43(6):1843-9. PubMed PMID: 12036988.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions. AU - Lehmann,Ordan J, AU - Ebenezer,Neil D, AU - Ekong,Rosemary, AU - Ocaka,Louise, AU - Mungall,Andrew J, AU - Fraser,Scott, AU - McGill,James I, AU - Hitchings,Roger A, AU - Khaw,Peng T, AU - Sowden,Jane C, AU - Povey,Sue, AU - Walter,Michael A, AU - Bhattacharya,Shomi S, AU - Jordan,Tim, PY - 2002/5/31/pubmed PY - 2002/6/22/medline PY - 2002/5/31/entrez SP - 1843 EP - 9 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 43 IS - 6 N2 - PURPOSE: Mutations in the forkhead transcription factor gene FOXC1 on 6p25 cause a range of ocular developmental abnormalities, with associated glaucoma. However, FOXC1 mutations have not been found in all similarly affected pedigrees mapping to this interval. This study was undertaken to investigate the potential role of 6p25 rearrangements in causing such phenotypes. METHODS: Two large families with autosomal dominant iris hypoplasia and early-onset glaucoma, 21 probands with Axenfeld-Rieger phenotypes not attributable to PITX2 mutations, and 7 individuals with documented 6p25 cytogenetic rearrangements, were investigated by genotyping and fluorescence in situ hybridization, with markers and probes from the 6p25 region. RESULTS: Interstitial 6p25 duplications were present in the unrelated families with iris hypoplasia, whereas an interstitial 6p25 deletion was identified in one Axenfeld-Rieger pedigree. Larger cytogenetic rearrangements, leading to trisomy or monosomy of the 6p25 region, resulted in microcornea and Rieger syndrome phenotypes, respectively. All the rearrangements encompassed FOXC1, increasing or decreasing the number of FOXC1 copies present, and appeared to correlate with the phenotypes observed. CONCLUSIONS: These findings represent the first example of both interstitial duplications and deletions cosegregating with a human developmental disorder that is attributable to altered dose of transcription factor. The data presented provide additional evidence for the pathogenicity of altered gene dosage of FOXC1 and suggest that a common mechanism is responsible for rearrangements of 6p25. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/12036988/Ocular_developmental_abnormalities_and_glaucoma_associated_with_interstitial_6p25_duplications_and_deletions_ L2 - https://iovs.arvojournals.org/article.aspx?volume=43&issue=6&page=1843 DB - PRIME DP - Unbound Medicine ER -