Introduction Frontonasal dysplasia (FND) consists of a group of disorders characterized by ocular hypertelorism, midline facial cleft affecting the nose and/or upper lip and palate, notching or clefting of the alae nasi, and it is sometimes associated with anterior cranium bifidum and other malformations (Wu et al. 2007; Kayserili et al. 2009; Twigg et al. 2009). Although it has long been recognized that FND results from abnormal development of the embryonic frontonasal prominence, which forms from cranial neural crest cells populating in between the forebrain and surface ectoderm and ultimately gives rise to the forehead, nose, philtrum, and premaxillary component of the upper jaw, the causes and molecular mechanisms of FND pathogenesis are not well understood (Farlie et al. 2016). Mutations in 5 genes, including ALX1, ALX3, ALX4, EFNB1, and ZSWIM6, have been identified in a small number of patients with FND disorders (

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Background:The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity.Methods:To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively.Results:There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10–2.04 and HR 2.16, 95%CI 1.24–3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele.Conclusion:The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers.

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