Munier, Francis L. and Frueh, Beatrice E. and Othenin-Girard, Philippe and Uffer, Sylvie and Cousin, Pascal and Wang, Ming X and Heon, Elise and Black, Graeme C. M. and Blasi, Maria A. and Balestrazzi, Emilio and Lorenz, Birgit and Escoto, Rafael and Barraquer, Rafael and Hoeltzenbein, Maria and Gloor, Balder and Fossarello, Maurizio and Singh, Arun D. and Arsenijevic, Yvan and Zografos, Leonidas and Schorderet, Daniel F. (2002) BIGH3 mutation spectrum in corneal dystrophies. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 43 (4). pp. 949-954. ISSN 0146-0404
Full text not available from this repository. (Request a copy)Abstract
PURPOSE. To investigate the molecular pathology underlying BIGH3-related corneal dystrophies (CDs) and to further delineate genotype-phenotype specificity. METHODS. Sixty-one index patients with CDs were subjected to phenotypic and genotypic characterization, The corneal phenotypes of all patients were assessed by biomicroscopy and documented by slit lamp photography. The BIGH3 gene was amplified exon by exon from constitutional DNA to perform single-strand conformation polymorphism (SSCP) analysis, followed by direct bidirectional sequencing of abnormal conformers. RESULTS. The phenotypes of CDs were classified as lattice CD in 30 patients, Groenouw type I in 12 (CDGGI), Avellino in (CDA), Reis-Buckler in 8 (CDRB), and Thiel-Behnke in 4 (CDTB). Fifty occurrences of 16 distinct mutations were identified, including 8 novel mutations responsible for lattice type IIIA in three patients (CDLIIA), intermediate type I/IIIA (CDLI/IIIA) in four patients. and atypical CDL with deep deposits in one patient (CDL-deep). CONCLUSIONS. Disease-causing mutations were identified in 80% of the patients (50/61). All mutations localize in two regions of kerato-epithelin: the amino acid R124 and BIGH3 fasc domain 4. This study also confirms the mutation hot spot at positions R124 and R555 with nearly 50% of the mutations targeting these two amino acids (24/50). In addition the corneal phenotypes induced by changes at R124 and R555 are amino acid specific: R124C in CDLI, R555W and R124S in CDGGI, R124H in CDA, R124L in CRRB, and R555Q in CDTB. In CDLIIIA, CDLI/IIIA, and CDL-deep the genotype-phenotype correlation is domain specific, with all changes occurring at the boundary or within the fasc4 domain.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | KERATO-EPITHELIN MUTATIONS; STROMAL DYSTROPHY; SEQUENCE-ANALYSIS; FASCICLIN-I; TGFBI GENE; EXPRESSION; BETA-IG-H3; GRASSHOPPER; EXON-14; BETA; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Nov 2021 14:00 |
| Last Modified: | 02 Nov 2021 14:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40423 |
Actions (login required)
 |
View Item |
