Browsing by Author "Britto, Ajit Denis"

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    Variable Expressivity with Apparent Reduced/Non-Penetrance in Crouzon Syndrome
    (1998) Britto, Ajit Denis; Hartsfield, James K., Jr.; Everett, Eric T.; Dean, Jeffrey A.; Shanks, James C.
    Objective: To determine whether specific mutations within the fibroblast growth factor receptor 2 (FGFR2) gene associated with Crouzon syndrome cause a phenotype with extreme variability of expression suggesting non-penetrance in clinically normal appearing individuals. Methods: Most mutations responsible for Crouzon syndrome occur in exons IIIa(U) or IIIc(B) of the FGFR2 gene, facilitating allelotyping by using polymerase chain reaction to mediate mutation analysis. Once a specific mutation is identified in the index case, remaining affected family members and clinically normal first-degree relatives are screened in order to correlate genotype with phenotype. Results: A novel missense mutation, a G to T transversion, involving the first base of codon 362 (Ala362Ser), was identified following DNA sequencing of exon IIIc, and a specific restriction fragment length polymorphism following BstNI enzyme digestion was found in all Crouzon-affected family members and in one clinically normal-appearing parent. Pattern profile analysis demonstrated a consistent collection of abnormal cephalometric measurements in the Crouzon affected family members, and to a lesser degree, in the clinically normal parent. Conclusion: We have identified a novel missense mutation in the FGFR2 gene predicting an Ala362Ser substitution that is shared by all family members affected by Crouzon syndrome, and a clinically normal appearing father. These data support non-penetrance of Crouzon syndrome.