gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

Molecular genetic analysis in the BIGH3 gene in lattice and granular corneal dystrophy: Is indirect mutation analysis recommended?

Meeting Abstract

  • corresponding author C. Grünauer-Kloevekorn - Klinik und Poliklinik für Augenheilkunde der Martin-Luther-Universität Halle, Halle/Saale
  • S. Bräutigam - Institut für Humangenetik der Universität Leipzig, Leipzig
  • M. J. M. Groh - Traunstein
  • U. Froster - Institut für Humangenetik der Universität Leipzig, Leipzig
  • G. I. W. Duncker - Klinik und Poliklinik für Augenheilkunde der Martin-Luther-Universität Halle, Halle/Saale

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogDO.08.03

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Veröffentlicht: 22. September 2004

© 2004 Grünauer-Kloevekorn et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Mutations of the BIGH3 gene were delineated as the underlying gene defect for for corneal dystrophy Lattice Type I (CDL1) and corneal dystrophy Avellino type (CDA) in families with different regional provenance. Point mutations in exon 4 with single base pair substitiution result in genetic code alterations Arg124Cys (CDL1) and ARG124His are described as hot spots. We report on histopathological and molecular genetic investigations in 2 German families with CDL1 and CDA.

Methods

In 3 affected family members and 1 unaffected family member of each family with CDL1 and CDA mutation analysis in exon 4 of BIGH3 gene by direct sequencing of genomic DNA from peripheral blood was performed. Histopathological examination of corneal tissue of both index patients was performed after penetrating keratoplasty.

Results

We revealed a heterocygous single base pair substituion 370C->T in family A (CDL1) and a heterocygous single base pair substitution 371G->A in family B(CDA). In both index patients diagnosis was confirmed by histopathological examination of corneal tissue. The sequencing results were confirmed by restriction digestion with HpyCH4V (NEB; CDL1) restriction endonuclease site and AvaII (NEB; CDA) restriction endonuclease site. The heterozygous 370C->T transition in family A alters the genetic code from Arg124Cys while heterozygous 371G->A transition in family B alters the genetic code from Arg124His in the BIGH3 gene.

Conclusions

Codon 124 of the BIGH3 gene appears as a mutation hot spot also in German families with CDL1 and CDA. Indirect mutation analysis with restriction digestion is suggested as first step investigation in those families. Direct sequencing of all exons is recommended as a second step if there are no results in restriction digestion.