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Eur J Hum Genet. 2014 Jan;22(1):136-9. doi: 10.1038/ejhg.2013.56. Epub 2013 Apr 10.

Somatic mosaicism in trichorhinophalangeal syndrome: a lesson for genetic counseling.

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  • 1Département 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.
  • 2Diagenos, Center for Medical Genetics, Osnabrück, Germany.
  • 31] 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.
  • 4Laboratoire de Génétique Chromosomique, Plate-forme puces à ADN, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
  • 5Service de Génétique Clinique et Moléculaire, Hospices Civils de Lyon, Lyon, France.
  • 6Département de Chirurgie Orthopédique Infantile, CHRU de Montpellier, Montpellier, France.
  • 7Département de Pédiatrie Endocrinologique, CHRU de Montpellier, Montpellier, France.

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.

PMID:
23572024
[PubMed - indexed for MEDLINE]
PMCID:
PMC3865400
Free PMC Article
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