Mutational spectrum of the oral-facial-digital type I syndrome: A study on a large collection of patients

Clelia Prattichizzo, Marina Macca, Valeria Novelli, Giovanna Giorgio, Adriano Barra, Brunella Franco, F. Abdulla, M. Abramowicz, S. Amy, I. Schafer, A. Bankier, S. White, M. G. Barcina, L. E. Bartoshesky, K. Jenny, F. A. Beemer, P. Benke, R. C. Betz, G. Bianchini, L. GaravelliS. Bigoni, L. Bird, J. Chibuk, D. Masser-Frye, N. Brunetti, A. Scarcella, H. G. Brunner, J. Burn, R. Carmi, C. Castellan, P. Castelluccio, B. Castle, M. A. Chiong, E. M. Cutiongco, F. Collins, E. Couchon, A. Curry, M. Pastore, C. Curry, A. Swenerton, T. Treisman, J. Dean, K. Devriendt, G. Matthijs, J. W. Dunlap, V. Shashi, N. Elcioglu, P. Farndon, G. B. Ferrero, R. Ferrier, N. Foulds, J. M. Friedman, A. Gal, U. Orth, M. Gardner, O. Gerola, G. Gillessen-Kaesbach, F. Giuliano, C. Turc-Carel, E. Gödde, V. Graber, G. E. Graham, F. Gurrieri, L. Harbour, A. Henderson, E. Jones, H. Heran, T. Homfray, R. Taylor, E. Iwarsson, P. Jensen, A. Jezela-Stanek, S. Joss, G. Taylor, S. L. Keeling, R. Klatt, A. Teebi, M. Klehr-Martinelli, D. Kotzot, M. Lees, S. Loughlin, K. Lhotta, F. Macdonald, F. Mari, A. Renieri, S. Marlin, J. McGaughran, F. McKenzie, D. R. McLeod, A. Megarbane, C. R. Mota, J. Mucke, A. Tzschach, E. Obersztyn, R. Okhowat, A. Shinzel, R. Pfau, B. Pober, F. L. Raymond, E. Reich, T. Reimschisel, J. Robertson, J. Roggenbuck, A. Sabato, J. Sanchez Del Pozo, C. Schell-Apacik, E. Schwaab, A. Selicorni, S. Sell, S. Smithson, A. Stray-Pedersen, T. Tan, H. Thiese, J. Tol, O. Toprak, D. Trump, J. Whittaker, D. Williams, L. Zelante, B. Zoll

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Oral-facial-digital type I (OFDI) syndrome is a male-lethal X-linked dominant developmental disorder belonging to the heterogeneous group of oral-facial-digital syndromes (OFDS). OFDI is characterized by malformations of the face, oral cavity, and digits. Central nervous system (CNS) abnormalities and cystic kidney disease can also be part of this condition. This rare genetic disorder is due to mutations in the OFD1 gene that encodes a centrosome/basal body protein necessary for primary cilium assembly and for left-right axis determination, thus ascribing OFDI to the growing number of disorders associated to ciliary dysfunction. We now report a mutation analysis study in a cohort of 100 unrelated affected individuals collected worldwide. Putative disease-causing mutations were identified in 81 patients (81%). We describe 67 different mutations, 64 of which represent novel mutations, including 36 frameshift, nine missense, 11 splice-site, and 11 nonsense mutations. Most of them concentrate in exons 3, 8, 9, 12, 13, and 16, suggesting that these exons may represent mutational hotspots. Phenotypic characterization of the patients provided a better definition of the clinical features of OFDI syndrome. Our results indicate that renal cystic disease is present in 60% of cases >18 years of age. Genotype-phenotype correlation did not reveal significant associations apart for the high-arched/cleft palate most frequently associated to missense and splice-site mutations. Our results contribute to further expand our knowledge on the molecular basis of OFDI syndrome.

Original languageEnglish
Pages (from-to)1237-1246
Number of pages10
JournalHuman Mutation
Volume29
Issue number10
DOIs
Publication statusPublished - Oct 2008

Fingerprint

Orofaciodigital Syndromes
Mutation
Cystic Kidney Diseases
Exons
Nervous System Malformations
Basal Bodies
Centrosome
Inborn Genetic Diseases
Cilia
Nonsense Codon
Genetic Association Studies
Cleft Palate
Mouth
Central Nervous System

Keywords

  • Mutation analysis
  • OFD1
  • OFDI
  • Primary ciliary dysfunction
  • X-linked dominant male lethal

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Mutational spectrum of the oral-facial-digital type I syndrome : A study on a large collection of patients. / Prattichizzo, Clelia; Macca, Marina; Novelli, Valeria; Giorgio, Giovanna; Barra, Adriano; Franco, Brunella; Abdulla, F.; Abramowicz, M.; Amy, S.; Schafer, I.; Bankier, A.; White, S.; Barcina, M. G.; Bartoshesky, L. E.; Jenny, K.; Beemer, F. A.; Benke, P.; Betz, R. C.; Bianchini, G.; Garavelli, L.; Bigoni, S.; Bird, L.; Chibuk, J.; Masser-Frye, D.; Brunetti, N.; Scarcella, A.; Brunner, H. G.; Burn, J.; Carmi, R.; Castellan, C.; Castelluccio, P.; Castle, B.; Chiong, M. A.; Cutiongco, E. M.; Collins, F.; Couchon, E.; Curry, A.; Pastore, M.; Curry, C.; Swenerton, A.; Treisman, T.; Dean, J.; Devriendt, K.; Matthijs, G.; Dunlap, J. W.; Shashi, V.; Elcioglu, N.; Farndon, P.; Ferrero, G. B.; Ferrier, R.; Foulds, N.; Friedman, J. M.; Gal, A.; Orth, U.; Gardner, M.; Gerola, O.; Gillessen-Kaesbach, G.; Giuliano, F.; Turc-Carel, C.; Gödde, E.; Graber, V.; Graham, G. E.; Gurrieri, F.; Harbour, L.; Henderson, A.; Jones, E.; Heran, H.; Homfray, T.; Taylor, R.; Iwarsson, E.; Jensen, P.; Jezela-Stanek, A.; Joss, S.; Taylor, G.; Keeling, S. L.; Klatt, R.; Teebi, A.; Klehr-Martinelli, M.; Kotzot, D.; Lees, M.; Loughlin, S.; Lhotta, K.; Macdonald, F.; Mari, F.; Renieri, A.; Marlin, S.; McGaughran, J.; McKenzie, F.; McLeod, D. R.; Megarbane, A.; Mota, C. R.; Mucke, J.; Tzschach, A.; Obersztyn, E.; Okhowat, R.; Shinzel, A.; Pfau, R.; Pober, B.; Raymond, F. L.; Reich, E.; Reimschisel, T.; Robertson, J.; Roggenbuck, J.; Sabato, A.; Sanchez Del Pozo, J.; Schell-Apacik, C.; Schwaab, E.; Selicorni, A.; Sell, S.; Smithson, S.; Stray-Pedersen, A.; Tan, T.; Thiese, H.; Tol, J.; Toprak, O.; Trump, D.; Whittaker, J.; Williams, D.; Zelante, L.; Zoll, B.

In: Human Mutation, Vol. 29, No. 10, 10.2008, p. 1237-1246.

Research output: Contribution to journalArticle

Prattichizzo, C, Macca, M, Novelli, V, Giorgio, G, Barra, A, Franco, B, Abdulla, F, Abramowicz, M, Amy, S, Schafer, I, Bankier, A, White, S, Barcina, MG, Bartoshesky, LE, Jenny, K, Beemer, FA, Benke, P, Betz, RC, Bianchini, G, Garavelli, L, Bigoni, S, Bird, L, Chibuk, J, Masser-Frye, D, Brunetti, N, Scarcella, A, Brunner, HG, Burn, J, Carmi, R, Castellan, C, Castelluccio, P, Castle, B, Chiong, MA, Cutiongco, EM, Collins, F, Couchon, E, Curry, A, Pastore, M, Curry, C, Swenerton, A, Treisman, T, Dean, J, Devriendt, K, Matthijs, G, Dunlap, JW, Shashi, V, Elcioglu, N, Farndon, P, Ferrero, GB, Ferrier, R, Foulds, N, Friedman, JM, Gal, A, Orth, U, Gardner, M, Gerola, O, Gillessen-Kaesbach, G, Giuliano, F, Turc-Carel, C, Gödde, E, Graber, V, Graham, GE, Gurrieri, F, Harbour, L, Henderson, A, Jones, E, Heran, H, Homfray, T, Taylor, R, Iwarsson, E, Jensen, P, Jezela-Stanek, A, Joss, S, Taylor, G, Keeling, SL, Klatt, R, Teebi, A, Klehr-Martinelli, M, Kotzot, D, Lees, M, Loughlin, S, Lhotta, K, Macdonald, F, Mari, F, Renieri, A, Marlin, S, McGaughran, J, McKenzie, F, McLeod, DR, Megarbane, A, Mota, CR, Mucke, J, Tzschach, A, Obersztyn, E, Okhowat, R, Shinzel, A, Pfau, R, Pober, B, Raymond, FL, Reich, E, Reimschisel, T, Robertson, J, Roggenbuck, J, Sabato, A, Sanchez Del Pozo, J, Schell-Apacik, C, Schwaab, E, Selicorni, A, Sell, S, Smithson, S, Stray-Pedersen, A, Tan, T, Thiese, H, Tol, J, Toprak, O, Trump, D, Whittaker, J, Williams, D, Zelante, L & Zoll, B 2008, 'Mutational spectrum of the oral-facial-digital type I syndrome: A study on a large collection of patients', Human Mutation, vol. 29, no. 10, pp. 1237-1246. https://doi.org/10.1002/humu.20792
Prattichizzo, Clelia ; Macca, Marina ; Novelli, Valeria ; Giorgio, Giovanna ; Barra, Adriano ; Franco, Brunella ; Abdulla, F. ; Abramowicz, M. ; Amy, S. ; Schafer, I. ; Bankier, A. ; White, S. ; Barcina, M. G. ; Bartoshesky, L. E. ; Jenny, K. ; Beemer, F. A. ; Benke, P. ; Betz, R. C. ; Bianchini, G. ; Garavelli, L. ; Bigoni, S. ; Bird, L. ; Chibuk, J. ; Masser-Frye, D. ; Brunetti, N. ; Scarcella, A. ; Brunner, H. G. ; Burn, J. ; Carmi, R. ; Castellan, C. ; Castelluccio, P. ; Castle, B. ; Chiong, M. A. ; Cutiongco, E. M. ; Collins, F. ; Couchon, E. ; Curry, A. ; Pastore, M. ; Curry, C. ; Swenerton, A. ; Treisman, T. ; Dean, J. ; Devriendt, K. ; Matthijs, G. ; Dunlap, J. W. ; Shashi, V. ; Elcioglu, N. ; Farndon, P. ; Ferrero, G. B. ; Ferrier, R. ; Foulds, N. ; Friedman, J. M. ; Gal, A. ; Orth, U. ; Gardner, M. ; Gerola, O. ; Gillessen-Kaesbach, G. ; Giuliano, F. ; Turc-Carel, C. ; Gödde, E. ; Graber, V. ; Graham, G. E. ; Gurrieri, F. ; Harbour, L. ; Henderson, A. ; Jones, E. ; Heran, H. ; Homfray, T. ; Taylor, R. ; Iwarsson, E. ; Jensen, P. ; Jezela-Stanek, A. ; Joss, S. ; Taylor, G. ; Keeling, S. L. ; Klatt, R. ; Teebi, A. ; Klehr-Martinelli, M. ; Kotzot, D. ; Lees, M. ; Loughlin, S. ; Lhotta, K. ; Macdonald, F. ; Mari, F. ; Renieri, A. ; Marlin, S. ; McGaughran, J. ; McKenzie, F. ; McLeod, D. R. ; Megarbane, A. ; Mota, C. R. ; Mucke, J. ; Tzschach, A. ; Obersztyn, E. ; Okhowat, R. ; Shinzel, A. ; Pfau, R. ; Pober, B. ; Raymond, F. L. ; Reich, E. ; Reimschisel, T. ; Robertson, J. ; Roggenbuck, J. ; Sabato, A. ; Sanchez Del Pozo, J. ; Schell-Apacik, C. ; Schwaab, E. ; Selicorni, A. ; Sell, S. ; Smithson, S. ; Stray-Pedersen, A. ; Tan, T. ; Thiese, H. ; Tol, J. ; Toprak, O. ; Trump, D. ; Whittaker, J. ; Williams, D. ; Zelante, L. ; Zoll, B. / Mutational spectrum of the oral-facial-digital type I syndrome : A study on a large collection of patients. In: Human Mutation. 2008 ; Vol. 29, No. 10. pp. 1237-1246.
@article{a3a7278209494bf9b169ed5deb02e604,
title = "Mutational spectrum of the oral-facial-digital type I syndrome: A study on a large collection of patients",
abstract = "Oral-facial-digital type I (OFDI) syndrome is a male-lethal X-linked dominant developmental disorder belonging to the heterogeneous group of oral-facial-digital syndromes (OFDS). OFDI is characterized by malformations of the face, oral cavity, and digits. Central nervous system (CNS) abnormalities and cystic kidney disease can also be part of this condition. This rare genetic disorder is due to mutations in the OFD1 gene that encodes a centrosome/basal body protein necessary for primary cilium assembly and for left-right axis determination, thus ascribing OFDI to the growing number of disorders associated to ciliary dysfunction. We now report a mutation analysis study in a cohort of 100 unrelated affected individuals collected worldwide. Putative disease-causing mutations were identified in 81 patients (81{\%}). We describe 67 different mutations, 64 of which represent novel mutations, including 36 frameshift, nine missense, 11 splice-site, and 11 nonsense mutations. Most of them concentrate in exons 3, 8, 9, 12, 13, and 16, suggesting that these exons may represent mutational hotspots. Phenotypic characterization of the patients provided a better definition of the clinical features of OFDI syndrome. Our results indicate that renal cystic disease is present in 60{\%} of cases >18 years of age. Genotype-phenotype correlation did not reveal significant associations apart for the high-arched/cleft palate most frequently associated to missense and splice-site mutations. Our results contribute to further expand our knowledge on the molecular basis of OFDI syndrome.",
keywords = "Mutation analysis, OFD1, OFDI, Primary ciliary dysfunction, X-linked dominant male lethal",
author = "Clelia Prattichizzo and Marina Macca and Valeria Novelli and Giovanna Giorgio and Adriano Barra and Brunella Franco and F. Abdulla and M. Abramowicz and S. Amy and I. Schafer and A. Bankier and S. White and Barcina, {M. G.} and Bartoshesky, {L. E.} and K. Jenny and Beemer, {F. A.} and P. Benke and Betz, {R. C.} and G. Bianchini and L. Garavelli and S. Bigoni and L. Bird and J. Chibuk and D. Masser-Frye and N. Brunetti and A. Scarcella and Brunner, {H. G.} and J. Burn and R. Carmi and C. Castellan and P. Castelluccio and B. Castle and Chiong, {M. A.} and Cutiongco, {E. M.} and F. Collins and E. Couchon and A. Curry and M. Pastore and C. Curry and A. Swenerton and T. Treisman and J. Dean and K. Devriendt and G. Matthijs and Dunlap, {J. W.} and V. Shashi and N. Elcioglu and P. Farndon and Ferrero, {G. B.} and R. Ferrier and N. Foulds and Friedman, {J. M.} and A. Gal and U. Orth and M. Gardner and O. Gerola and G. Gillessen-Kaesbach and F. Giuliano and C. Turc-Carel and E. G{\"o}dde and V. Graber and Graham, {G. E.} and F. Gurrieri and L. Harbour and A. Henderson and E. Jones and H. Heran and T. Homfray and R. Taylor and E. Iwarsson and P. Jensen and A. Jezela-Stanek and S. Joss and G. Taylor and Keeling, {S. L.} and R. Klatt and A. Teebi and M. Klehr-Martinelli and D. Kotzot and M. Lees and S. Loughlin and K. Lhotta and F. Macdonald and F. Mari and A. Renieri and S. Marlin and J. McGaughran and F. McKenzie and McLeod, {D. R.} and A. Megarbane and Mota, {C. R.} and J. Mucke and A. Tzschach and E. Obersztyn and R. Okhowat and A. Shinzel and R. Pfau and B. Pober and Raymond, {F. L.} and E. Reich and T. Reimschisel and J. Robertson and J. Roggenbuck and A. Sabato and {Sanchez Del Pozo}, J. and C. Schell-Apacik and E. Schwaab and A. Selicorni and S. Sell and S. Smithson and A. Stray-Pedersen and T. Tan and H. Thiese and J. Tol and O. Toprak and D. Trump and J. Whittaker and D. Williams and L. Zelante and B. Zoll",
year = "2008",
month = "10",
doi = "10.1002/humu.20792",
language = "English",
volume = "29",
pages = "1237--1246",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

TY - JOUR

T1 - Mutational spectrum of the oral-facial-digital type I syndrome

T2 - A study on a large collection of patients

AU - Prattichizzo, Clelia

AU - Macca, Marina

AU - Novelli, Valeria

AU - Giorgio, Giovanna

AU - Barra, Adriano

AU - Franco, Brunella

AU - Abdulla, F.

AU - Abramowicz, M.

AU - Amy, S.

AU - Schafer, I.

AU - Bankier, A.

AU - White, S.

AU - Barcina, M. G.

AU - Bartoshesky, L. E.

AU - Jenny, K.

AU - Beemer, F. A.

AU - Benke, P.

AU - Betz, R. C.

AU - Bianchini, G.

AU - Garavelli, L.

AU - Bigoni, S.

AU - Bird, L.

AU - Chibuk, J.

AU - Masser-Frye, D.

AU - Brunetti, N.

AU - Scarcella, A.

AU - Brunner, H. G.

AU - Burn, J.

AU - Carmi, R.

AU - Castellan, C.

AU - Castelluccio, P.

AU - Castle, B.

AU - Chiong, M. A.

AU - Cutiongco, E. M.

AU - Collins, F.

AU - Couchon, E.

AU - Curry, A.

AU - Pastore, M.

AU - Curry, C.

AU - Swenerton, A.

AU - Treisman, T.

AU - Dean, J.

AU - Devriendt, K.

AU - Matthijs, G.

AU - Dunlap, J. W.

AU - Shashi, V.

AU - Elcioglu, N.

AU - Farndon, P.

AU - Ferrero, G. B.

AU - Ferrier, R.

AU - Foulds, N.

AU - Friedman, J. M.

AU - Gal, A.

AU - Orth, U.

AU - Gardner, M.

AU - Gerola, O.

AU - Gillessen-Kaesbach, G.

AU - Giuliano, F.

AU - Turc-Carel, C.

AU - Gödde, E.

AU - Graber, V.

AU - Graham, G. E.

AU - Gurrieri, F.

AU - Harbour, L.

AU - Henderson, A.

AU - Jones, E.

AU - Heran, H.

AU - Homfray, T.

AU - Taylor, R.

AU - Iwarsson, E.

AU - Jensen, P.

AU - Jezela-Stanek, A.

AU - Joss, S.

AU - Taylor, G.

AU - Keeling, S. L.

AU - Klatt, R.

AU - Teebi, A.

AU - Klehr-Martinelli, M.

AU - Kotzot, D.

AU - Lees, M.

AU - Loughlin, S.

AU - Lhotta, K.

AU - Macdonald, F.

AU - Mari, F.

AU - Renieri, A.

AU - Marlin, S.

AU - McGaughran, J.

AU - McKenzie, F.

AU - McLeod, D. R.

AU - Megarbane, A.

AU - Mota, C. R.

AU - Mucke, J.

AU - Tzschach, A.

AU - Obersztyn, E.

AU - Okhowat, R.

AU - Shinzel, A.

AU - Pfau, R.

AU - Pober, B.

AU - Raymond, F. L.

AU - Reich, E.

AU - Reimschisel, T.

AU - Robertson, J.

AU - Roggenbuck, J.

AU - Sabato, A.

AU - Sanchez Del Pozo, J.

AU - Schell-Apacik, C.

AU - Schwaab, E.

AU - Selicorni, A.

AU - Sell, S.

AU - Smithson, S.

AU - Stray-Pedersen, A.

AU - Tan, T.

AU - Thiese, H.

AU - Tol, J.

AU - Toprak, O.

AU - Trump, D.

AU - Whittaker, J.

AU - Williams, D.

AU - Zelante, L.

AU - Zoll, B.

PY - 2008/10

Y1 - 2008/10

N2 - Oral-facial-digital type I (OFDI) syndrome is a male-lethal X-linked dominant developmental disorder belonging to the heterogeneous group of oral-facial-digital syndromes (OFDS). OFDI is characterized by malformations of the face, oral cavity, and digits. Central nervous system (CNS) abnormalities and cystic kidney disease can also be part of this condition. This rare genetic disorder is due to mutations in the OFD1 gene that encodes a centrosome/basal body protein necessary for primary cilium assembly and for left-right axis determination, thus ascribing OFDI to the growing number of disorders associated to ciliary dysfunction. We now report a mutation analysis study in a cohort of 100 unrelated affected individuals collected worldwide. Putative disease-causing mutations were identified in 81 patients (81%). We describe 67 different mutations, 64 of which represent novel mutations, including 36 frameshift, nine missense, 11 splice-site, and 11 nonsense mutations. Most of them concentrate in exons 3, 8, 9, 12, 13, and 16, suggesting that these exons may represent mutational hotspots. Phenotypic characterization of the patients provided a better definition of the clinical features of OFDI syndrome. Our results indicate that renal cystic disease is present in 60% of cases >18 years of age. Genotype-phenotype correlation did not reveal significant associations apart for the high-arched/cleft palate most frequently associated to missense and splice-site mutations. Our results contribute to further expand our knowledge on the molecular basis of OFDI syndrome.

AB - Oral-facial-digital type I (OFDI) syndrome is a male-lethal X-linked dominant developmental disorder belonging to the heterogeneous group of oral-facial-digital syndromes (OFDS). OFDI is characterized by malformations of the face, oral cavity, and digits. Central nervous system (CNS) abnormalities and cystic kidney disease can also be part of this condition. This rare genetic disorder is due to mutations in the OFD1 gene that encodes a centrosome/basal body protein necessary for primary cilium assembly and for left-right axis determination, thus ascribing OFDI to the growing number of disorders associated to ciliary dysfunction. We now report a mutation analysis study in a cohort of 100 unrelated affected individuals collected worldwide. Putative disease-causing mutations were identified in 81 patients (81%). We describe 67 different mutations, 64 of which represent novel mutations, including 36 frameshift, nine missense, 11 splice-site, and 11 nonsense mutations. Most of them concentrate in exons 3, 8, 9, 12, 13, and 16, suggesting that these exons may represent mutational hotspots. Phenotypic characterization of the patients provided a better definition of the clinical features of OFDI syndrome. Our results indicate that renal cystic disease is present in 60% of cases >18 years of age. Genotype-phenotype correlation did not reveal significant associations apart for the high-arched/cleft palate most frequently associated to missense and splice-site mutations. Our results contribute to further expand our knowledge on the molecular basis of OFDI syndrome.

KW - Mutation analysis

KW - OFD1

KW - OFDI

KW - Primary ciliary dysfunction

KW - X-linked dominant male lethal

UR - http://www.scopus.com/inward/record.url?scp=55349129995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55349129995&partnerID=8YFLogxK

U2 - 10.1002/humu.20792

DO - 10.1002/humu.20792

M3 - Article

C2 - 18546297

AN - SCOPUS:55349129995

VL - 29

SP - 1237

EP - 1246

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 10

ER -