@article {194,
	title = {De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay.},
	journal = {Am J Hum Genet},
	volume = {96},
	year = {2015},
	month = {2015 Mar 05},
	pages = {462-73},
	abstract = {<p>Freeman-Sheldon syndrome, or distal arthrogryposis type 2A (DA2A), is an autosomal-dominant condition caused by mutations in MYH3 and characterized by multiple congenital contractures of the face and limbs and normal cognitive development. We identified a subset of five individuals who had been putatively diagnosed with "DA2A with severe neurological abnormalities" and for whom congenital contractures of the limbs and face, hypotonia, and global developmental delay had resulted in early death in three cases; this is a unique condition that we now refer to as CLIFAHDD syndrome. Exome sequencing identified missense mutations in the sodium leak channel, non-selective (NALCN) in four families affected by CLIFAHDD syndrome. We used molecular-inversion probes to screen for NALCN in a cohort of 202 distal arthrogryposis (DA)-affected individuals as well as concurrent exome sequencing of six other DA-affected individuals, thus revealing NALCN mutations in ten additional families with "atypical" forms of DA. All 14 mutations were missense variants predicted to alter amino acid residues in or near the S5 and S6 pore-forming segments of NALCN, highlighting the functional importance of these segments. In vitro functional studies demonstrated that NALCN alterations nearly abolished the expression of wild-type NALCN, suggesting that alterations that cause CLIFAHDD syndrome have a dominant-negative effect. In contrast, homozygosity for mutations in other regions of NALCN has been reported in three families affected by an autosomal-recessive condition characterized mainly by hypotonia and severe intellectual disability. Accordingly, mutations in NALCN can cause either a recessive or dominant condition characterized by varied though overlapping phenotypic features, perhaps based on the type of mutation and affected protein domain(s).</p>},
	keywords = {Arthrogryposis, Contracture, Craniofacial Dysostosis, Cytoskeletal Proteins, Exome, Extremities, Face, Female, Gene Frequency, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Infant, Male, Muscle Hypotonia, Mutation, Missense, Sodium Channels},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2015.01.003},
	author = {Chong, Jessica X and McMillin, Margaret J and Shively, Kathryn M and Beck, Anita E and Marvin, Colby T and Armenteros, Jose R and Buckingham, Kati J and Nkinsi, Naomi T and Boyle, Evan A and Berry, Margaret N and Bocian, Maureen and Foulds, Nicola and Uzielli, Maria Luisa Giovannucci and Haldeman-Englert, Chad and Hennekam, Raoul C M and Kaplan, Paige and Kline, Antonie D and Mercer, Catherine L and Nowaczyk, Malgorzata J M and Klein Wassink-Ruiter, Jolien S and McPherson, Elizabeth W and Moreno, Regina A and Scheuerle, Angela E and Shashi, Vandana and Stevens, Cathy A and Carey, John C and Monteil, Arnaud and Lory, Philippe and Tabor, Holly K and Smith, Joshua D and Shendure, Jay and Nickerson, Deborah A and Bamshad, Michael J}
}
@article {256,
	title = {Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5.},
	journal = {Am J Hum Genet},
	volume = {94},
	year = {2014},
	month = {2014 May 01},
	pages = {734-44},
	abstract = {<p>Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83\%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82\%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher{\textquoteright}s exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition. </p>},
	keywords = {Abnormalities, Multiple, Arachnodactyly, Arthrogryposis, Blepharophimosis, Child, Child, Preschool, Cleft Palate, Clubfoot, Connective Tissue Diseases, Contracture, Exome, Female, Hand Deformities, Congenital, Humans, Ion Channels, Male, Mutation, Ophthalmoplegia, Pedigree, Retinal Diseases},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2014.03.015},
	author = {McMillin, Margaret J and Beck, Anita E and Chong, Jessica X and Shively, Kathryn M and Buckingham, Kati J and Gildersleeve, Heidi I S and Aracena, Mariana I and Aylsworth, Arthur S and Bitoun, Pierre and Carey, John C and Clericuzio, Carol L and Crow, Yanick J and Curry, Cynthia J and Devriendt, Koenraad and Everman, David B and Fryer, Alan and Gibson, Kate and Giovannucci Uzielli, Maria Luisa and Graham, John M and Hall, Judith G and Hecht, Jacqueline T and Heidenreich, Randall A and Hurst, Jane A and Irani, Sarosh and Krapels, Ingrid P C and Leroy, Jules G and Mowat, David and Plant, Gordon T and Robertson, Stephen P and Schorry, Elizabeth K and Scott, Richard H and Seaver, Laurie H and Sherr, Elliott and Splitt, Miranda and Stewart, Helen and Stumpel, Constance and Temel, Sehime G and Weaver, David D and Whiteford, Margo and Williams, Marc S and Tabor, Holly K and Smith, Joshua D and Shendure, Jay and Nickerson, Deborah A and Bamshad, Michael J}
}
