title: Somatic mosaicism in trichorhinophalangeal syndrome: a lesson for genetic counseling.
abstract: Trichorhinophalangeal syndrome type I (TRPSI) is a genetic disorder characterized by sparse hair, a bulbous nasal tip, short stature with severe generalized shortening of all phalanges, metacarpal and metatarsal bones and cone-shaped epiphyses. This syndrome is caused by autosomal dominant mutations in the TRPS1 gene. However, because recurrence has been observed in siblings from healthy parents, an autosomal recessive mode of inheritance has also been suggested. We report on a male patient, born to healthy unrelated parents, with TRPSI. Using Sanger sequencing, we identified a mutation in the TRPS1 gene (c.2735 G>A, P.Cys912Tyr). The same mutation was detected as a 10% mosaic mutation by Pyrosequencing in blood-derived DNA from his healthy mother. To our knowledge, this is the first time that somatic mosaicism has been identified in TRPSI. This data combined with the observations of recurrences in siblings from healthy parents modifies the genetic counseling for TRPSI, which should discuss a 5-10 percent recurrence risk for healthy parents with an affected child because of the possibility of germinal mosaicism.
authors.affiliation: Département de Génétique Médicale, Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Sud-Languedoc Roussillon, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Corsini
authors.affiliation: Diagenos, Center for Medical Genetics, Osnabrück, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gencik
authors.affiliation: Département de Génétique Médicale, Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Sud-Languedoc Roussillon, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
authors.forename: Marjolaine
authors.initials: M
authors.lastname: Willems
authors.affiliation: Diagenos, Center for Medical Genetics, Osnabrück, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Decker
authors.affiliation: 1] Département de Génétique Médicale, Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Sud-Languedoc Roussillon, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France [2] Unité INSERM U844, Institut des Neurosciences de Montpellier, Montpellier, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Sanchez
authors.affiliation: Laboratoire de Génétique Chromosomique, Plate-forme puces à ADN, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Puechberty
authors.affiliation: Laboratoire de Génétique Chromosomique, Plate-forme puces à ADN, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
authors.forename: Anouck
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Laboratoire de Génétique Chromosomique, Plate-forme puces à ADN, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Girard
authors.affiliation: Service de Génétique Clinique et Moléculaire, Hospices Civils de Lyon, Lyon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Edery
authors.affiliation: Service de Génétique Clinique et Moléculaire, Hospices Civils de Lyon, Lyon, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bretonnes
authors.affiliation: Département de Chirurgie Orthopédique Infantile, CHRU de Montpellier, Montpellier, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cottalorda
authors.affiliation: Laboratoire de Génétique Chromosomique, Plate-forme puces à ADN, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Lefort
authors.affiliation: Département de Pédiatrie Endocrinologique, CHRU de Montpellier, Montpellier, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Jeandel
authors.affiliation: Département de Génétique Médicale, Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Sud-Languedoc Roussillon, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.affiliation: 1] Département de Génétique Médicale, Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Sud-Languedoc Roussillon, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France [2] Unité INSERM U844, Institut des Neurosciences de Montpellier, Montpellier, France.
authors.forename: David
authors.initials: D
authors.lastname: Genevieve
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005385:Fingers / Q000002:abnormalities* / Q000473:pathology; D005817:Genetic Counseling; D006201:Hair Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D015826:Langer-Giedion Syndrome / Q000235:genetics* / Q000473:pathology; D008297:Male; D009030:Mosaicism; D009666:Nose / Q000002:abnormalities* / Q000473:pathology; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D014157:Transcription Factors