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

Abstract

Synostosis is the premature fusion of cranial sutures in the brain vaultproducing continued growth at the position of the open cranium suturein parallel to brain growth resulting in morphological deformation calledCraniosynostosis. It is observed in 1/2100-1/2500 live births, occurring inboth syndromic and non-syndromic forms and addressed in approximately180 different syndromes. Recent studies have shown that notably in 20% ofcases are caused by single gene mutations or chromosome abnormalities.FGFR2, FGFR3, TWIST1 and EFNB1 are listed to be the most common causativegenes in craniosynostosis, though rarely involved many others likeFGFR1, MSX2 are already known and growing number of novel genes are intenselybeing identi����ied. Mutations in FGFR2, FGFR3, TWIST1 are involved insyndromic and lesser extent in non syndromic forms while EFNB1 are solelyrecognized to be associated with Craniofrontonasal Syndrome (CFNS).Thirty craniosynostosis patients, except CFNS, where chromosomal abnormalitieswere previously excluded, are recruited to our research study withtheir families. Our work����low will be targeted mutation screening for commongenes, FGFR2 and FGFR3, mutation negative patients will be subjectto deletion/duplication analysis by craniofrontonasal MLPA kit, which willfollow by MSX2 sequencing and targeted mutation screening for FGFR1.Our investigation is ongoing presently. We anticipate that our results willfoster the acknowledged molecular diagnostic ����low charts in craniosynostosisand further delineate genotype-phenotype relationship. Unde����ined caseswill be esteemed subjects for novel gene identi����ication by next generationsequencing.