@article {386,
	title = {De novo mutations in inhibitors of Wnt, BMP, and Ras/ERK signaling pathways in non-syndromic midline craniosynostosis.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {114},
	year = {2017},
	month = {2017 08 29},
	pages = {E7341-E7347},
	abstract = {<p>Non-syndromic craniosynostosis (NSC) is a frequent congenital malformation in which one or more cranial sutures fuse prematurely. Mutations causing rare syndromic craniosynostoses in humans and engineered mouse models commonly increase signaling of the Wnt, bone morphogenetic protein (BMP), or Ras/ERK pathways, converging on shared nuclear targets that promote bone formation. In contrast, the genetics of NSC is largely unexplored. More than 95\% of NSC is sporadic, suggesting a role for de novo mutations. Exome sequencing of 291 parent-offspring trios with midline NSC revealed 15 probands with heterozygous damaging de novo mutations in 12 negative regulators of Wnt, BMP, and Ras/ERK signaling (10.9-fold enrichment,  = 2.4 {\texttimes} 10).  had 4 de novo and 14 transmitted mutations; no other gene had more than 1. Four familial NSC kindreds had mutations in genes previously implicated in syndromic disease. Collectively, these mutations contribute to 10\% of probands. Mutations are predominantly loss-of-function, implicating haploinsufficiency as a frequent mechanism. A common risk variant near  increased the penetrance of  mutations and was overtransmitted to patients with de novo mutations in other genes in these pathways, supporting a frequent two-locus pathogenesis. These findings implicate new genes in NSC and demonstrate related pathophysiology of common non-syndromic and rare syndromic craniosynostoses. These findings have implications for diagnosis, risk of recurrence, and risk of adverse neurodevelopmental outcomes. Finally, the use of pathways identified in rare syndromic disease to find genes accounting for non-syndromic cases may prove broadly relevant to understanding other congenital disorders featuring high locus heterogeneity.</p>},
	keywords = {Adult, Animals, Bone Morphogenetic Proteins, Child, Child, Preschool, Cranial Sutures, Craniosynostoses, Exome, Female, Humans, Male, MAP Kinase Signaling System, Mutation, Osteogenesis, Penetrance, Phenotype, ras Proteins, Sequence Analysis, DNA, Signal Transduction, Smad6 Protein, Whole Exome Sequencing},
	issn = {1091-6490},
	doi = {10.1073/pnas.1709255114},
	author = {Timberlake, Andrew T and Furey, Charuta G and Choi, Jungmin and Nelson-Williams, Carol and Loring, Erin and Galm, Amy and Kahle, Kristopher T and Steinbacher, Derek M and Larysz, Dawid and Persing, John A and Lifton, Richard P}
}
@article {190,
	title = {Somatic Activating RAS Mutations Cause Vascular Tumors Including Pyogenic Granuloma.},
	journal = {J Invest Dermatol},
	volume = {135},
	year = {2015},
	month = {2015 Jun},
	pages = {1698-1700},
	keywords = {Adolescent, Cell Proliferation, Child, Child, Preschool, Female, Gene Expression Regulation, Neoplastic, Granuloma, Pyogenic, Humans, Infant, Infant, Newborn, Male, Mutation, ras Proteins, Vascular Neoplasms},
	issn = {1523-1747},
	doi = {10.1038/jid.2015.55},
	author = {Lim, Young H and Douglas, Stephanie R and Ko, Christine J and Antaya, Richard J and McNiff, Jennifer M and Zhou, Jing and Choate, Keith A and Narayan, Deepak}
}
@article {286,
	title = {Somatic HRAS p.G12S mutation causes woolly hair and epidermal nevi.},
	journal = {J Invest Dermatol},
	volume = {134},
	year = {2014},
	month = {2014 Apr},
	pages = {1149-1152},
	keywords = {Adherens Junctions, Child, Exome, Female, Genes, ras, Hair, Hair Diseases, Hair Follicle, Humans, Intermediate Filaments, Mosaicism, Mutation, Nevus, Phenotype, ras Proteins, Sequence Analysis, DNA, Signal Transduction},
	issn = {1523-1747},
	doi = {10.1038/jid.2013.430},
	author = {Levinsohn, Jonathan L and Teng, Joyce and Craiglow, Brittany G and Loring, Erin C and Burrow, T Andrew and Mane, Shrikant S and Overton, John D and Lifton, Richard P and McNiff, Jennifer M and Lucky, Anne W and Choate, Keith A}
}
@article {318,
	title = {Whole-exome sequencing reveals somatic mutations in HRAS and KRAS, which cause nevus sebaceus.},
	journal = {J Invest Dermatol},
	volume = {133},
	year = {2013},
	month = {2013 Mar},
	pages = {827-830},
	keywords = {Adolescent, Adult, Amino Acid Sequence, Biopsy, Child, Child, Preschool, Cohort Studies, Epidermis, Exome, Humans, Infant, Middle Aged, Molecular Sequence Data, Mutation, Nevus, Sebaceous of Jadassohn, Proto-Oncogene Proteins, Proto-Oncogene Proteins p21(ras), ras Proteins, Sequence Analysis, DNA, Young Adult},
	issn = {1523-1747},
	doi = {10.1038/jid.2012.379},
	author = {Levinsohn, Jonathan L and Tian, Li C and Boyden, Lynn M and McNiff, Jennifer M and Narayan, Deepak and Loring, Erin S and Yun, Duri and Sugarman, Jeffrey L and Overton, John D and Mane, Shrikant M and Lifton, Richard P and Paller, Amy S and Wagner, Annette M and Antaya, Richard J and Choate, Keith A}
}
