RESUMO
Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P ≤ 5 × 10-8): rs781716 (P = 4.71 × 10-9; odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 × 10-8; OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 × 10-9; OR = 0.34), located ~ 155 kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 × 10-8, OR = 0.45; P = 3.31 × 10-8, OR = 0.45; P = 1.09 × 10-8, OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 × 10-8, OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 × 10-6). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821-55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.
Assuntos
Proteína Morfogenética Óssea 7/genética , Craniossinostoses/genética , Variação Genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Metilação de DNA , Genes Reporter , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Íntrons/genética , Desequilíbrio de Ligação , Regiões Promotoras Genéticas/genética , Fatores de RiscoRESUMO
AIM: The purpose of this study was to retrospectively evaluate the efficacy of the developed by the authors surgical technique in patients with a radiographically confirmed diagnosis of sagittal craniosynostosis. MATERIAL AND METHODS: 34 children with scaphocephaly underwent surgical treatment with the authors' operative technique. Quantitative assessments of the operative results, based on the preoperative and postoperative (1 year after the procedure) measurements of the cephalic index (cranial width / cranial length x 100), were performed in all patients. RESULTS: The presented original authors' surgical technique resulted in a significantly good skull shape immediately after the procedure. The mean preoperative cephalic index was 64.5, and the mean immediate postoperative index- 75.0, yielding a mean improvement of 10.5. There were no intraoperative complications. One case required a small postoperative correction. CONCLUSION: The presented operative technique provides immediate and significant surgical correction of the head shape, demonstrated by quantitative measurements using the cephalic index and by photographs.