@article {422,
	title = {Mutations in Fibronectin Cause a Subtype of Spondylometaphyseal Dysplasia with "Corner Fractures".},
	journal = {Am J Hum Genet},
	volume = {101},
	year = {2017},
	month = {2017 Nov 02},
	pages = {815-823},
	abstract = {<p>Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of collagens, fibrillin-1, and other proteins. It is also known to play roles in skeletal tissues through its secretion by osteoblasts, chondrocytes, and mesenchymal cells. Spondylometaphyseal dysplasias (SMDs) comprise a diverse group of skeletal dysplasias and often manifest as short stature, growth-plate irregularities, and vertebral anomalies, such as scoliosis. By comparing the exomes of individuals with SMD with the radiographic appearance of "corner fractures" at metaphyses, we identified three individuals with fibronectin (FN1) variants affecting highly conserved residues. Furthermore, using matching tools and the SkelDys emailing list, we identified other individuals with de novo~FN1 variants and a similar phenotype. The severe scoliosis in most individuals and rare developmental coxa vara distinguish individuals with FN1 mutations from those with classical Sutcliffe-type SMD. To study functional consequences of these FN1 mutations on the protein level, we introduced three disease-associated missense variants (p.Cys87Phe [c.260G>T], p.Tyr240Asp [c.718T>G], and p.Cys260Gly [c.778T>G]) into a recombinant secreted N-terminal 70~kDa fragment (rF70K) and the full-length fibronectin (rFN). The wild-type rF70K and rFN were secreted into the culture medium, whereas all mutant proteins were either not secreted or secreted at significantly lower amounts. Immunofluorescence analysis demonstrated increased intracellular retention of the mutant proteins. In summary, FN1 mutations that cause defective fibronectin secretion are found in SMD, and we thus provide additional evidence for a critical function of fibronectin in cartilage and bone.</p>},
	keywords = {Adolescent, Adult, Bone and Bones, Bone Diseases, Developmental, Cartilage, Child, Child, Preschool, Exome, Female, Fibronectins, Fractures, Bone, Humans, Male, Mutation, Osteochondrodysplasias, Phenotype, Scoliosis},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2017.09.019},
	author = {Lee, Chae Syng and Fu, He and Baratang, Nissan and Rousseau, Justine and Kumra, Heena and Sutton, V Reid and Niceta, Marcello and Ciolfi, Andrea and Yamamoto, Guilherme and Bertola, D{\'e}bora and Marcelis, Carlo L and Lugtenberg, Dorien and Bartuli, Andrea and Kim, Choel and Hoover-Fong, Julie and Sobreira, Nara and Pauli, Richard and Bacino, Carlos and Krakow, Deborah and Parboosingh, Jillian and Yap, Patrick and Kariminejad, Ariana and McDonald, Marie T and Aracena, Mariana I and Lausch, Ekkehart and Unger, Sheila and Superti-Furga, Andrea and Lu, James T and Cohn, Dan H and Tartaglia, Marco and Lee, Brendan H and Reinhardt, Dieter P and Campeau, Philippe M}
}
@article {275,
	title = {Mutations in PCYT1A, encoding a key regulator of phosphatidylcholine metabolism, cause spondylometaphyseal dysplasia with cone-rod dystrophy.},
	journal = {Am J Hum Genet},
	volume = {94},
	year = {2014},
	month = {2014 Jan 02},
	pages = {105-12},
	keywords = {Alleles, Child, Preschool, Choline-Phosphate Cytidylyltransferase, Female, Humans, Infant, Male, Middle Aged, Mutation, Missense, Osteochondrodysplasias, Pedigree, Phosphatidylcholines, Retinitis Pigmentosa},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2013.11.018},
	author = {Hoover-Fong, Julie and Sobreira, Nara and Jurgens, Julie and Modaff, Peggy and Blout, Carrie and Moser, Ann and Kim, Ok-Hwa and Cho, Tae-Joon and Cho, Sung Yoon and Kim, Sang Jin and Jin, Dong-Kyu and Kitoh, Hiroshi and Park, Woong-Yang and Ling, Hua and Hetrick, Kurt N and Doheny, Kimberly F and Valle, David and Pauli, Richard M}
}
