Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease
Posterior microphthalmos (MCOP) is a rare isolated developmental anomaly of the eye characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal-recessive form (arMCOP) of the disease. Based on published linkage data, we re...
Published in: | The American Journal of Human Genetics |
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Main Authors: | , , , , , , , , , , , , , , , , |
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2011
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Online Access: | https://curis.ku.dk/portal/da/publications/autosomalrecessive-posterior-microphthalmos-is-caused-by-mutations-in-prss56-a-gene-encoding-a-trypsinlike-serine-protease(a918533a-52fc-4b02-bf19-5d4db2299523).html https://doi.org/10.1016/j.ajhg.2011.02.006 |
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ftcopenhagenunip:oai:pure.atira.dk:publications/a918533a-52fc-4b02-bf19-5d4db2299523 2023-12-17T10:29:59+01:00 Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease Gal, Andreas Rau, Isabella El Matri, Leila Kreienkamp, Hans-Jürgen Fehr, Susanne Baklouti, Karim Chouchane, Ibtissem Li, Yun Rehbein, Monika Fuchs, Josefine Fledelius, Hans C Vilhelmsen, Kaj Schorderet, Daniel F Munier, Francis L Ostergaard, Elsebet Thompson, Debra A Rosenberg, Thomas 2011 https://curis.ku.dk/portal/da/publications/autosomalrecessive-posterior-microphthalmos-is-caused-by-mutations-in-prss56-a-gene-encoding-a-trypsinlike-serine-protease(a918533a-52fc-4b02-bf19-5d4db2299523).html https://doi.org/10.1016/j.ajhg.2011.02.006 eng eng info:eu-repo/semantics/restrictedAccess Gal , A , Rau , I , El Matri , L , Kreienkamp , H-J , Fehr , S , Baklouti , K , Chouchane , I , Li , Y , Rehbein , M , Fuchs , J , Fledelius , H C , Vilhelmsen , K , Schorderet , D F , Munier , F L , Ostergaard , E , Thompson , D A & Rosenberg , T 2011 , ' Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease ' , American Journal of Human Genetics , vol. 88 , no. 3 , pp. 382-90 . https://doi.org/10.1016/j.ajhg.2011.02.006 article 2011 ftcopenhagenunip https://doi.org/10.1016/j.ajhg.2011.02.006 2023-11-22T23:59:09Z Posterior microphthalmos (MCOP) is a rare isolated developmental anomaly of the eye characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal-recessive form (arMCOP) of the disease. Based on published linkage data, we refined the position of the disease locus (MCOP6) in an interval of 250 kb in chromosome 2q37.1 in two large Faroese families. We detected three different mutations in PRSS56. Patients of the Faroese families were either homozygous for c.926G>C (p.Trp309Ser) or compound heterozygous for c.926G>C and c.526C>G (p.Arg176Gly), whereas a homozygous 1 bp duplication (c.1066dupC) was identified in five patients with arMCOP from a consanguineous Tunisian family. In one patient with MCOP from the Faroe Islands and in another one from Turkey, no PRSS56 mutation was detected, suggesting nonallelic heterogeneity of the trait. Using RT-PCR, PRSS56 transcripts were detected in samples derived from the human adult retina, cornea, sclera, and optic nerve. The expression of the mouse ortholog could be first detected in the eye at E17 and was maintained into adulthood. The predicted PRSS56 protein is a 603 amino acid long secreted trypsin-like serine peptidase. The c.1066dupC is likely to result in a functional null allele, whereas the two point mutations predict the replacement of evolutionary conserved and functionally important residues. Molecular modeling of the p.Trp309Ser mutant suggests that both the affinity and reactivity of the enzyme toward in vivo protein substrates are likely to be substantially reduced. Article in Journal/Newspaper Faroe Islands University of Copenhagen: Research Faroe Islands The American Journal of Human Genetics 88 3 382 390 |
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University of Copenhagen: Research |
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ftcopenhagenunip |
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English |
description |
Posterior microphthalmos (MCOP) is a rare isolated developmental anomaly of the eye characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal-recessive form (arMCOP) of the disease. Based on published linkage data, we refined the position of the disease locus (MCOP6) in an interval of 250 kb in chromosome 2q37.1 in two large Faroese families. We detected three different mutations in PRSS56. Patients of the Faroese families were either homozygous for c.926G>C (p.Trp309Ser) or compound heterozygous for c.926G>C and c.526C>G (p.Arg176Gly), whereas a homozygous 1 bp duplication (c.1066dupC) was identified in five patients with arMCOP from a consanguineous Tunisian family. In one patient with MCOP from the Faroe Islands and in another one from Turkey, no PRSS56 mutation was detected, suggesting nonallelic heterogeneity of the trait. Using RT-PCR, PRSS56 transcripts were detected in samples derived from the human adult retina, cornea, sclera, and optic nerve. The expression of the mouse ortholog could be first detected in the eye at E17 and was maintained into adulthood. The predicted PRSS56 protein is a 603 amino acid long secreted trypsin-like serine peptidase. The c.1066dupC is likely to result in a functional null allele, whereas the two point mutations predict the replacement of evolutionary conserved and functionally important residues. Molecular modeling of the p.Trp309Ser mutant suggests that both the affinity and reactivity of the enzyme toward in vivo protein substrates are likely to be substantially reduced. |
format |
Article in Journal/Newspaper |
author |
Gal, Andreas Rau, Isabella El Matri, Leila Kreienkamp, Hans-Jürgen Fehr, Susanne Baklouti, Karim Chouchane, Ibtissem Li, Yun Rehbein, Monika Fuchs, Josefine Fledelius, Hans C Vilhelmsen, Kaj Schorderet, Daniel F Munier, Francis L Ostergaard, Elsebet Thompson, Debra A Rosenberg, Thomas |
spellingShingle |
Gal, Andreas Rau, Isabella El Matri, Leila Kreienkamp, Hans-Jürgen Fehr, Susanne Baklouti, Karim Chouchane, Ibtissem Li, Yun Rehbein, Monika Fuchs, Josefine Fledelius, Hans C Vilhelmsen, Kaj Schorderet, Daniel F Munier, Francis L Ostergaard, Elsebet Thompson, Debra A Rosenberg, Thomas Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease |
author_facet |
Gal, Andreas Rau, Isabella El Matri, Leila Kreienkamp, Hans-Jürgen Fehr, Susanne Baklouti, Karim Chouchane, Ibtissem Li, Yun Rehbein, Monika Fuchs, Josefine Fledelius, Hans C Vilhelmsen, Kaj Schorderet, Daniel F Munier, Francis L Ostergaard, Elsebet Thompson, Debra A Rosenberg, Thomas |
author_sort |
Gal, Andreas |
title |
Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease |
title_short |
Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease |
title_full |
Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease |
title_fullStr |
Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease |
title_full_unstemmed |
Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease |
title_sort |
autosomal-recessive posterior microphthalmos is caused by mutations in prss56, a gene encoding a trypsin-like serine protease |
publishDate |
2011 |
url |
https://curis.ku.dk/portal/da/publications/autosomalrecessive-posterior-microphthalmos-is-caused-by-mutations-in-prss56-a-gene-encoding-a-trypsinlike-serine-protease(a918533a-52fc-4b02-bf19-5d4db2299523).html https://doi.org/10.1016/j.ajhg.2011.02.006 |
geographic |
Faroe Islands |
geographic_facet |
Faroe Islands |
genre |
Faroe Islands |
genre_facet |
Faroe Islands |
op_source |
Gal , A , Rau , I , El Matri , L , Kreienkamp , H-J , Fehr , S , Baklouti , K , Chouchane , I , Li , Y , Rehbein , M , Fuchs , J , Fledelius , H C , Vilhelmsen , K , Schorderet , D F , Munier , F L , Ostergaard , E , Thompson , D A & Rosenberg , T 2011 , ' Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease ' , American Journal of Human Genetics , vol. 88 , no. 3 , pp. 382-90 . https://doi.org/10.1016/j.ajhg.2011.02.006 |
op_rights |
info:eu-repo/semantics/restrictedAccess |
op_doi |
https://doi.org/10.1016/j.ajhg.2011.02.006 |
container_title |
The American Journal of Human Genetics |
container_volume |
88 |
container_issue |
3 |
container_start_page |
382 |
op_container_end_page |
390 |
_version_ |
1785582875029012480 |