Genotype and clinical care correlations in craniosynostosis: Findings from a cohort of 630 australian and new zealand patients

Roscioli T., Elakis G., Cox T.C., Moon D.J., Venselaar H., Turner A.M., Le T., Hackett E., Haan E., Colley A., Mowat D., Worgan L., Kirk E.P., Sachdev R., Thompson E., Gabbett M., Mcgaughran J., Gibson K., Gattas M., Freckmann M.-L., Dixon J., Hoefsloot L., Field M., Hackett A., Kamien B., Edwards M., Ades L.C., Collins F.A., Wilson M.J., Savarirayan R., Tan T.Y., Amor D.J., Mcgillivray G., White S.M., Glass I.A., David D.J., Anderson P.J., Gianoutsos M. and Buckley M.F. (2013) Genotype and clinical care correlations in craniosynostosis: Findings from a cohort of 630 australian and new zealand patients. American Journal of Medical Genetics, Part C: Seminars in Medical Genetics, 163 4: 259-270. doi:10.1002/ajmg.c.31378

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Author Roscioli T.
Elakis G.
Cox T.C.
Moon D.J.
Venselaar H.
Turner A.M.
Le T.
Hackett E.
Haan E.
Colley A.
Mowat D.
Worgan L.
Kirk E.P.
Sachdev R.
Thompson E.
Gabbett M.
Mcgaughran J.
Gibson K.
Gattas M.
Freckmann M.-L.
Dixon J.
Hoefsloot L.
Field M.
Hackett A.
Kamien B.
Edwards M.
Ades L.C.
Collins F.A.
Wilson M.J.
Savarirayan R.
Tan T.Y.
Amor D.J.
Mcgillivray G.
White S.M.
Glass I.A.
David D.J.
Anderson P.J.
Gianoutsos M.
Buckley M.F.
Title Genotype and clinical care correlations in craniosynostosis: Findings from a cohort of 630 australian and new zealand patients
Journal name American Journal of Medical Genetics, Part C: Seminars in Medical Genetics   Check publisher's open access policy
ISSN 1552-4868
1552-4876
Publication date 2013
Sub-type Article (original research)
DOI 10.1002/ajmg.c.31378
Volume 163
Issue 4
Start page 259
End page 270
Total pages 12
Place of publication Hoboken, NJ, U.S.A.
Publisher Jossey Bass, Ed. & Pub.
Collection year 2014
Language eng
Subject 2716 Genetics (clinical)
1311 Genetics
Abstract Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis.
Keyword Apert
Crouzon
Fibroblast growth factor receptor
Muenke
Pfeiffer
Saethre-Chotzen
TWIST1
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
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Created: Thu, 10 Apr 2014, 13:26:17 EST by Matthew Lamb on behalf of School of Medicine