European Human Genetics Conference 2013, Paris, France, 8 - 11 June 2013, vol.21, no.1, 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 identiied. 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 worklow 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. Undeined cases
will be esteemed subjects for novel gene identiication by next generation