title: Nail-Patella Syndrome: clinical and molecular data in 55 families raising the hypothesis of a genetic heterogeneity.
abstract: Nail-Patella Syndrome (NPS) is a rare autosomal dominant condition comprising nail and skeletal anomalies. Skeletal features include dysplastic patellae and iliac horns, as well as scapula and elbow dysplasia. Nephropathy and glaucoma or intra-ocular hypertension can sometimes be present. NPS is due to variants affecting function in LMX1B, which encodes a LIM-homeodomain protein critical for limb, kidney and eye development. We describe the phenotype and the molecular data of 55 index patients and their 39 relatives presenting with typical NPS. We identified 38 different LMX1B anomalies, 19 of which were not reported before. In our series, 9% of families are not carriers of a LMX1B genomic alteration after extensive study of the coding and non-coding regions of the gene. One of the families showed no linkage to the LMX1B locus, raising the hypothesis of a genetic heterogeneity.
authors.affiliation: Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France.|Faculté de Médecine, Université Lille Nord de France, Lille, France.
authors.forename: Jamal
authors.identifier: http://orcid.org/0000-0002-7111-0050
authors.initials: J
authors.lastname: Ghoumid
authors.affiliation: Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France.|Faculté de Médecine, Université Lille Nord de France, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Petit
authors.affiliation: Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France.|Faculté de Médecine, Université Lille Nord de France, Lille, France.|Clinical Genetics Department, Guy's Hospital, London, UK.
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.affiliation: Laboratoire de Biologie Moléculaire, Centre de Biologie-Pathologie, CHRU, Lille, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Jourdain
authors.affiliation: Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France.
authors.forename: José
authors.initials: J
authors.lastname: Guerra
authors.affiliation: Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dieux-Coeslier
authors.affiliation: Functional and Structural Genomic Platform, Université Lille 2, Lille, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.affiliation: Faculté de Médecine, Université Lille Nord de France, Lille, France.|Clinical Genetics Department, Guy's Hospital, London, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.affiliation: Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France.|Faculté de Médecine, Université Lille Nord de France, Lille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Manouvrier-Hanu
authors.affiliation: Clinical Genetics Department, Guy's Hospital, London, UK.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Escande
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D015870:Gene Expression; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D005901:Glaucoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007085:Ilium / Q000002:abnormalities / Q000378:metabolism; D007438:Introns; D060850:LIM-Homeodomain Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009261:Nail-Patella Syndrome / Q000235:genetics* / Q000473:pathology; D009262:Nails / Q000378:metabolism / Q000473:pathology; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000473:pathology; D009798:Ocular Hypertension / Q000235:genetics* / Q000473:pathology; D010329:Patella / Q000002:abnormalities / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D012540:Scapula / Q000002:abnormalities / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors