@article {340,
	title = {Loss-of-Function Mutations in YY1AP1 Lead to Grange Syndrome and a Fibromuscular Dysplasia-Like Vascular Disease.},
	journal = {Am J Hum Genet},
	volume = {100},
	year = {2017},
	month = {2017 Jan 05},
	pages = {21-30},
	abstract = {<p>Fibromuscular dysplasia (FMD) is a heterogeneous group of non-atherosclerotic and non-inflammatory arterial diseases that primarily involves the renal and cerebrovascular arteries. Grange syndrome is an autosomal-recessive condition characterized by severe and early-onset vascular disease similar to FMD and variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities. Exome-sequencing analysis of DNA from three affected siblings with Grange syndrome identified compound heterozygous nonsense variants in YY1AP1, and homozygous nonsense or frameshift YY1AP1 variants were subsequently identified in additional unrelated probands with Grange syndrome. YY1AP1 encodes yin yang 1 (YY1)-associated protein 1 and is an activator of the YY1 transcription factor. We determined that YY1AP1 localizes to the nucleus and is a component of the INO80 chromatin remodeling complex, which is responsible for transcriptional regulation, DNA repair, and replication. Molecular studies revealed that loss of YY1AP1 in vascular smooth muscle cells leads to cell cycle arrest with decreased proliferation and increased levels of the cell cycle regulator p21/WAF/CDKN1A and disrupts TGF-β-driven differentiation of smooth muscle cells. Identification of YY1AP1 mutations as a cause of FMD indicates that this condition can result from underlying genetic variants that significantly alter the phenotype of vascular smooth muscle cells.</p>},
	keywords = {Adolescent, Adult, Bone and Bones, Brachydactyly, Cell Cycle Checkpoints, Exome, Female, Fibromuscular Dysplasia, Genes, Recessive, Heterozygote, Homozygote, Humans, Learning Disorders, Male, Middle Aged, Muscle, Smooth, Vascular, Mutation, Nuclear Proteins, Pedigree, Syndactyly, Syndrome, Transcription Factors},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2016.11.008},
	author = {Guo, Dong-Chuan and Duan, Xue-Yan and Regalado, Ellen S and Mellor-Crummey, Lauren and Kwartler, Callie S and Kim, Dong and Lieberman, Kenneth and de Vries, Bert B A and Pfundt, Rolph and Schinzel, Albert and Kotzot, Dieter and Shen, Xuetong and Yang, Min-Lee and Bamshad, Michael J and Nickerson, Deborah A and Gornik, Heather L and Ganesh, Santhi K and Braverman, Alan C and Grange, Dorothy K and Milewicz, Dianna M}
}
@article {213,
	title = {Dominant De Novo Mutations in GJA1 Cause Erythrokeratodermia Variabilis et Progressiva, without Features of Oculodentodigital Dysplasia.},
	journal = {J Invest Dermatol},
	volume = {135},
	year = {2015},
	month = {2015 Jun},
	pages = {1540-1547},
	abstract = {<p>Genetic investigation of inherited skin disorders has informed the understanding of skin self-renewal, differentiation, and barrier function. Erythrokeratodermia variabilis et progressiva (EKVP) is a rare, inherited skin disease that is characterized by transient figurate patches of erythema, localized or generalized scaling, and frequent palmoplantar keratoderma. By using exome sequencing, we show that de novo missense mutations in GJA1 (gap junction protein alpha 1) cause EKVP. The severe, progressive skin disease in EKVP subjects with GJA1 mutations is distinct from limited cutaneous findings rarely found in the systemic disorder oculodentodigital dysplasia, also caused by dominant GJA1 mutations. GJA1 encodes connexin 43 (Cx43), the most widely expressed gap junction protein. We show that the GJA1 mutations in EKVP subjects lead to disruption of Cx43 membrane localization and aggregation within the Golgi. These findings reveal a critical role for Cx43 in epidermal homeostasis, and they provide evidence of organ-specific pathobiology resulting from different mutations within GJA1. </p>},
	keywords = {Amino Acid Sequence, Cell Membrane, Child, Child, Preschool, Connexin 43, Connexins, Craniofacial Abnormalities, Disease Progression, Erythrokeratodermia Variabilis, Exome, Eye Abnormalities, Female, Foot Deformities, Congenital, Golgi Apparatus, HeLa Cells, Humans, Immunohistochemistry, Male, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation, Phenotype, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Skin Diseases, Syndactyly, Tooth Abnormalities},
	issn = {1523-1747},
	doi = {10.1038/jid.2014.485},
	author = {Boyden, Lynn M and Craiglow, Brittany G and Zhou, Jing and Hu, Ronghua and Loring, Erin C and Morel, Kimberly D and Lauren, Christine T and Lifton, Richard P and Bilguvar, Kaya and Paller, Amy S and Choate, Keith A}
}
