title: ADAMTSL4-associated isolated ectopia lentis: Further patients, novel mutations and a detailed phenotype description.
abstract: ADAMTSL4 mutations seem to be the most common cause of isolated ectoplia lentis (EL) and thus are important concerning the differential diagnosis of connective tissue syndromes with EL as main feature. In this study, we describe an additional cohort of patients with apparently isolated EL. All underwent a detailed clinical exam with cardiac evaluation combined with ADAMTSL4 mutation analysis. Mutations were identified in 12/15 patients with EL. Besides the European founder mutation p. (Gln256Profs*38) we identified five further mutations not yet described in the literature: p. (Leu249Tyrfs*21), p. (Ala388Glyfs*8), p. (Arg746His), p. (Gly592Ser), and p. (Arg865His). Clinical evaluation showed common additional ocular features such as high myopia, but no major systemic findings. In particular: no dilatation of the aortic root was reported on. This report increases the total number of patients with ADAMTSL4 mutations reported on today and reviews in detail the clinical findings in all patients reported on to date demonstrate, that these patients have a mainly ocular phenotype. There are no consistent systemic findings. The differentiation between syndromic and isolated EL is crucial for the further surveillance, treatment, and counseling of these patients, especially in young children.
authors.affiliation: MGZ Medizinisch Genetisches Zentrum, Munich, Germany.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Neuhann
authors.affiliation: MGZ Medizinisch Genetisches Zentrum, Munich, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Stegerer
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Riess
authors.affiliation: Department of Clinical Genetics, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
authors.forename: Edward
authors.initials: E
authors.lastname: Blair
authors.affiliation: Gemeinschaftspraxis für Humangenetik, Homburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Martin
authors.affiliation: Klinische Genetik, Universitätskinderklinik, Paracelsus Medizinische Privatuniversität, Salzburg, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wieser
authors.affiliation: Synlab MVZ Humangenetik Mannheim, Mannheim, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Kläs
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Bouman
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Alma
authors.initials: A
authors.lastname: Kuechler
authors.affiliation: Klinische Genetik, Universitätskinderklinik, Paracelsus Medizinische Privatuniversität, Salzburg, Austria.
authors.forename: Olaf
authors.initials: O
authors.lastname: Rittinger
mesh_terms: D000071096:ADAMTS Proteins; D000293:Adolescent; D000328:Adult; D001011:Aorta / Q000033:anatomy & histology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004479:Ectopia Lentis / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009216:Myopia / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D019699:Thrombospondins / Q000235:genetics*
chemical_list: C486779:ADAMTSL4 protein, human; D019699:Thrombospondins; D000071096:ADAMTS Proteins
keywords: ADAMTSL4; anterior segment malformations; aortic root dilatation; ectopia lentis; high myopia; marfan syndrome