@article {137,
	title = {Rare variants in the notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome.},
	journal = {Am J Med Genet A},
	volume = {167A},
	year = {2015},
	month = {2015 Nov},
	pages = {2795-9},
	abstract = {<p>Klippel-Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel-Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel-Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left-right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel-Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel{\textquoteright}s deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel-Feil syndrome, and in addition-from a mechanistic standpoint-suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. {\textcopyright} 2015 Wiley Periodicals, Inc. </p>},
	keywords = {Adolescent, Base Sequence, Female, Humans, Klippel-Feil Syndrome, Male, Molecular Sequence Data, Mutation, Pedigree, Radiography, Receptors, Notch, Signal Transduction, Spine},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.37263},
	author = {Karaca, Ender and Yuregir, Ozge O and Bozdogan, Sevcan T and Aslan, Huseyin and Pehlivan, Davut and Jhangiani, Shalini N and Akdemir, Zeynep C and Gambin, Tomasz and Bayram, Yavuz and Atik, Mehmed M and Erdin, Serkan and Muzny, Donna and Gibbs, Richard A and Lupski, James R}
}
@article {243,
	title = {Monoallelic and biallelic mutations in MAB21L2 cause a spectrum of major eye malformations.},
	journal = {Am J Hum Genet},
	volume = {94},
	year = {2014},
	month = {2014 Jun 05},
	pages = {915-23},
	abstract = {<p>We identified four different missense mutations in the single-exon gene MAB21L2 in eight individuals with bilateral eye malformations from five unrelated families via three independent exome sequencing projects. Three mutational events altered the same amino acid (Arg51), and two were identical de novo mutations (c.151C>T [p.Arg51Cys]) in unrelated children with bilateral anophthalmia, intellectual disability, and rhizomelic skeletal dysplasia. c.152G>A (p.Arg51His) segregated with autosomal-dominant bilateral colobomatous microphthalmia in a large multiplex family. The fourth heterozygous mutation (c.145G>A [p.Glu49Lys]) affected an amino acid within two residues of Arg51 in an adult male with bilateral colobomata. In a fifth family, a homozygous mutation (c.740G>A [p.Arg247Gln]) altering a different region of the protein was identified in two male siblings with bilateral retinal colobomata. In mouse embryos, Mab21l2 showed strong expression in the developing eye, pharyngeal arches, and limb bud. As predicted by structural homology, wild-type MAB21L2 bound single-stranded RNA, whereas this activity was lost in all altered forms of the protein. MAB21L2 had no detectable nucleotidyltransferase activity in~vitro, and its function remains unknown. Induced expression of wild-type MAB21L2 in human embryonic kidney 293 cells increased phospho-ERK (pERK1/2) signaling. Compared to the wild-type and p.Arg247Gln proteins, the proteins with the Glu49 and Arg51 variants had increased stability. Abnormal persistence of pERK1/2 signaling in MAB21L2-expressing cells during development is a plausible pathogenic mechanism for the heterozygous mutations. The phenotype associated with the homozygous mutation might be a consequence of complete loss of MAB21L2 RNA binding, although the cellular function of this interaction remains unknown. </p>},
	keywords = {Adult, Alleles, Animals, Anophthalmos, Brain Diseases, Metabolic, Inborn, Coloboma, Corneal Opacity, Exome, Eye Proteins, Female, Gene Expression, HEK293 Cells, Heterozygote, Homozygote, Humans, Intellectual Disability, Intracellular Signaling Peptides and Proteins, Male, Mice, Microcephaly, Microphthalmos, Mutation, Missense, Pedigree, Phenotype, Protein Conformation, Signal Transduction},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2014.05.005},
	author = {Rainger, Joe and Pehlivan, Davut and Johansson, Stefan and Bengani, Hemant and Sanchez-Pulido, Luis and Williamson, Kathleen A and Ture, Mehmet and Barker, Heather and Rosendahl, Karen and Spranger, J{\"u}rgen and Horn, Denise and Meynert, Alison and Floyd, James A B and Prescott, Trine and Anderson, Carl A and Rainger, Jacqueline K and Karaca, Ender and Gonzaga-Jauregui, Claudia and Jhangiani, Shalini and Muzny, Donna M and Seawright, Anne and Soares, Dinesh C and Kharbanda, Mira and Murday, Victoria and Finch, Andrew and Gibbs, Richard A and van Heyningen, Veronica and Taylor, Martin S and Yakut, Tahsin and Knappskog, Per M and Hurles, Matthew E and Ponting, Chris P and Lupski, James R and Houge, Gunnar and FitzPatrick, David R}
}
