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Clinical, molecular, and genotype–phenotype correlation studies from 25 cases of oral–facial–digital syndrome type 1: a French and Belgian collaborative study
  1. C Thauvin-Robinet1,
  2. M Cossée2,
  3. V Cormier-Daire3,
  4. L Van Maldergem4,
  5. A Toutain5,
  6. Y Alembik6,
  7. E Bieth7,
  8. V Layet8,
  9. P Parent9,
  10. A David10,
  11. A Goldenberg3,
  12. G Mortier11,
  13. D Héron12,
  14. P Sagot13,
  15. A M Bouvier14,
  16. F Huet15,
  17. V Cusin16,
  18. A Donzel16,
  19. D Devys2,
  20. J R Teyssier16,
  21. L Faivre
  1. 1Centre de Génétique, Hôpital d’Enfants, CHU Dijon, France
  2. 2Laboratoire de Diagnostic Génétique, CHRU Strasbourg, France
  3. 3Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France
  4. 4Institut de Pathologie et de Génétique, Loverval, Belgique
  5. 5Service de Génétique, CHU Tours, France
  6. 6Service de Génétique Médicale, Hôpital Hautepierre, CHU Strasbourg, France
  7. 7Laboratoire de Génétique, CHU Purpan, Toulouse, France
  8. 8Unité de Cytogénétique et Génétique médicale, CH Le Havre, France
  9. 9Département de Pédiatrie et de Génétique Médicale, CHU Brest, France
  10. 10Service de Génétique Médicale, CHU Nantes, France
  11. 11Centre de Génétique Médicale, Ghent, Belgique
  12. 12Département de Génétique Cytogénétique et Embryologie, Hôpital La Pitié-Salpétrière, Paris, France
  13. 13Clinique Gynécologique et Obstétrique, Maternité du Bocage, CHU Dijon, France
  14. 14Centre d’Investigation Clinique et d’Epidémiologie Clinique, Faculté de Médecine, Dijon, France
  15. 15Service de Pédiatrie 1, Hôpital d’Enfants, CHU Dijon, France
  16. 16Laboratoire de Génétique Moléculaire, Hôpital du Bocage, CHU Dijon, France
  1. Correspondence to:
 Dr C Thauvin-Robinet
 Centre de Génétique, Hôpital d’Enfants, 10 Bd maréchal de Lattre de Tassigny, 21034 Dijon cédex, France; christel.thauvin{at}


Oral–facial–digital syndrome type 1 (OFD1) is characterised by an X linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, tooth, and distal abnormalities, polycystic kidney disease, and central nervous system malformations. Large interfamilial and intrafamilial clinical variability has been widely reported, and 18 distinct mutations have been previously reported within OFD1. A French and Belgian collaborative study collected 25 cases from 16 families. OFD1 was analysed using direct sequencing and phenotype–genotype correlation was performed using χ2 test. X inactivation studies were performed on blood lymphocytes. In 11 families, 11 novel mutations, including nine frameshift, one nonsense, and one missense mutation were identified, which spanned nine different exons. A combination of our results with previously reported cases showed that the majority of mutations (65.5%) was located in exons 3, 8, 9, 13, and 16. There was phenotype–genotype correlation between (a) polycystic kidney disease and splice mutations; (b) mental retardation and mutations located in exons 3, 8, 9, 13, and 16; and (c) tooth abnormalities and mutations located in coiled coil domains. Comparing the phenotype of the families with a pathogenic mutation to families with absence of OFD1 mutation, polycystic kidneys and short stature were significantly more frequent in the group with no OFD1 mutation, whereas lingual hamartomas were significantly more frequent in the group with OFD1 mutation. Finally, an X inactivation study showed non-random X inactivation in a third of the samples. Differential X inactivation between mothers and daughters in two families with high intrafamilial variability was of particular interest. Slight phenotype–genotype correlations were established, and X inactivation study showed that skewed X inactivation could be partially involved in the pathogenesis of intrafamilial clinical variability.

  • CNS, central nervous system
  • OFD1, oral–facial–digital syndrome type 1
  • PKD, polycystic kidney disease
  • OFD1
  • dominant X linked mode of inheritance

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  • Competing interests: none declared