title: Retinitis pigmentosa, cutis laxa, and pseudoxanthoma elasticum-like skin manifestations associated with GGCX mutations.
abstract: Gamma-glutamyl carboxylase (GGCX) mutations have been reported in patients with a pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, and multiple vitamin K-dependent coagulation factor deficiencies. We report on the clinical findings and molecular results in 13 affected members of two families who had a uniform phenotype consisting of (PXE)-like skin manifestations in the neck and trunk, loose sagging skin of the trunk and upper limbs, and retinitis pigmentosa confirmed by electroretinographies in 10 affected individuals. There were no coagulation abnormalities. Molecular investigations of the ATP-binding cassette subfamily C member 6 did not yield causative mutations. All 13 affected family members were found to be homozygous for the splice-site mutation c.373+3G>T in the GGCX gene. All tested parents were heterozygous for the mutation, and healthy siblings were either heterozygous or had the wild type. We suggest that the present patients represent a hitherto unreported phenotype associated with GGCX mutations. Digenic inheritance has been suggested to explain the variability in phenotype in GGCX mutation carriers. Consequently, the present phenotype may not be explained only by the GGCX mutations only but may be influenced by variants in other genes or epigenetic and environmental factors.
authors.affiliation: Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran. Electronic address: arianakariminejad@yahoo.com.
authors.forename: Ariana
authors.initials: A
authors.lastname: Kariminejad
authors.affiliation: Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Bozorgmehr
authors.affiliation: Azad University Medical Branch, Tehran, Iran.
authors.forename: Abdolhamid
authors.initials: A
authors.lastname: Najafi
authors.affiliation: Mehrgan Genetic Center, Sari, Iran.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Khoshaeen
authors.affiliation: Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ghalandari
authors.affiliation: Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.affiliation: Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
authors.forename: Mohamad H
authors.initials: MH
authors.lastname: Kariminejad
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Vanakker
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Mohammad J
authors.initials: MJ
authors.lastname: Hosen
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Fransiska
authors.initials: F
authors.lastname: Malfait
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Quaglino
authors.affiliation: Department of Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Florijn
authors.affiliation: Department of Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands; Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Arthur A B
authors.initials: AAB
authors.lastname: Bergen
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Raoul C
authors.initials: RC
authors.lastname: Hennekam
mesh_terms: D000293:Adolescent; D000328:Adult; D019735:Carbon-Carbon Ligases / Q000235:genetics* / Q000378:metabolism; D002648:Child; D003483:Cutis Laxa / Q000235:genetics* / Q000473:pathology; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011561:Pseudoxanthoma Elasticum / Q000235:genetics* / Q000473:pathology; D022821:RNA Splice Sites / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D012867:Skin / Q000473:pathology; D014812:Vitamin K / Q000378:metabolism; D055815:Young Adult
chemical_list: D022821:RNA Splice Sites; D014812:Vitamin K; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase
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