Molecular Test Results of Syndromic Craniosynostosis Patients: genotype-phenotype correlations

Karaman V. , Altunoğlu U., Toksoy G. , Karaman B. , Kayserili Karabay H.

European Human Genetics Conference 2013, Paris, France, 8 - 11 June 2013, vol.21, no.1, pp.99

  • Publication Type: Conference Paper / Summary Text
  • Volume: 21
  • City: Paris
  • Country: France
  • Page Numbers: pp.99


Synostosis is the premature fusion of cranial sutures in the brain vault

producing continued growth at the position of the open cranium suture

in parallel to brain growth resulting in morphological deformation called

Craniosynostosis. It is observed in 1/2100-1/2500 live births, occurring in

both syndromic and non-syndromic forms and addressed in approximately

180 different syndromes. Recent studies have shown that notably in 20% of

cases are caused by single gene mutations or chromosome abnormalities.

FGFR2, FGFR3, TWIST1 and EFNB1 are listed to be the most common causative

genes in craniosynostosis, though rarely involved many others like

FGFR1, MSX2 are already known and growing number of novel genes are intensely

being identi􀏐ied. Mutations in FGFR2, FGFR3, TWIST1 are involved in

syndromic and lesser extent in non syndromic forms while EFNB1 are solely

recognized to be associated with Craniofrontonasal Syndrome (CFNS).

Thirty craniosynostosis patients, except CFNS, where chromosomal abnormalities

were previously excluded, are recruited to our research study with

their families. Our work􀏐low will be targeted mutation screening for common

genes, FGFR2 and FGFR3, mutation negative patients will be subject

to deletion/duplication analysis by craniofrontonasal MLPA kit, which will

follow by MSX2 sequencing and targeted mutation screening for FGFR1.

Our investigation is ongoing presently. We anticipate that our results will

foster the acknowledged molecular diagnostic 􀏐low charts in craniosynostosis

and further delineate genotype-phenotype relationship. Unde􀏐ined cases

will be esteemed subjects for novel gene identi􀏐ication by next generation