Analysis of the Variety of Sequence Variants of Cleft Lip and/or Palate Candidate Gene SOS1

Analysis of the Variety of Sequence Variants of Cleft Lip and/or Palate Candidate Gene SOS1

Ingrida Uktverytė, Laima Ambrozaitytė, Albertas Timinskas, Aušra Matulevičienė, Algirdas Utkus, Vaidutis Kučinskas

Background. Orofacial clefting (OFC) is developmental defect in the upper lip re­sulting from failure of the medial nasal process and/or incomplete fusion of the palatal shelves on either side. It is one of the most common birth defects. Incidence of OFC varies from 1/500 to 1/1000 births. In the population of Lithuania the incidence of OFC is 1/544 and this statis­tics is akin to Caucasian (European) pop­ulations statistics. The goal of this study was to find SOS1 gene’s sequence varii ants which may contribute to nonsyn- dromic cleft lip and/or palate (NS-CL/P) phenotype in Lithuanian population. 23 exons of SOS1 gene were analysed by direct sequencing because it gives oppor­tunity to find variants not only in coding but also in flanking sequences as NS-CL/P risk factors most probably are non patogenic mutations which usually cause complex phenotypes.

Material and methods. All 23 exons of SOS1 gene were sequenced for 30 patients with NS-CL/P and 60 controls.

Results. 19 different variants were identified, 15 of which are SNPs and four in/del polymorphisms. Allele and genotype frequencies are similar to other European populations (HapMap Project). j² test was performed to find statistically significant variants. One variant c.1075-98_1075-97 insGTG (rs56299761) near exon 9 shows statistical significance (j²=4.841; p=0.028), another variant c.2792-51_2792-50 insA near exon 18 was close to significance (j²=3.388; p=0.066).

Conclusion. Results of this study show SOS1 gene’s assocciation with NS-CL/P. SOS1 gene can be considered as candidate gene for NS-CL/P in the population of Lithuania according to this work results and known interaction with other candidate genes FGFR1, ERBB2, EGFR confirms its importance to NS-CL/P phenotype.

Keywords: nonsyndromic cleft lip and/or palate, SOS1 gene, sequence vari­ants, candidate gene, %² test.