@article {417, title = {Exome sequencing identifies a de novo frameshift mutation in the imprinted gene ZDBF2 in a sporadic patient with Nasopalpebral Lipoma-coloboma syndrome.}, journal = {Am J Med Genet A}, volume = {170}, year = {2016}, month = {2016 07}, pages = {1934-7}, abstract = {

Nasopalpebral lipoma-coloboma syndrome (NPLCS, OMIM\%167730) is an uncommon malformation entity with autosomal dominant inheritance characterized by the combination of nasopalpebral lipoma, colobomas in upper and lower eyelids, telecanthus, and maxillary hypoplasia. To date, no genetic defects have been associated with familial or sporadic NPLCS cases and the etiology of the disease remains unknown. In this work, the results of whole exome sequencing in a sporadic NPLCS patient are presented. Exome sequencing identified a de novo heterozygous frameshift dinucleotide insertion c.6245_6246 insTT (p.His2082fs*67) in ZDBF2 (zinc finger, DBF-type containing 2), a gene located at 2q33.3. This variant was absent in parental DNA, in a set of 300 ethnically matched controls, and in public exome variant databases. This is the first genetic variant identified in a NPLCS patient and evidence supporting the pathogenicity of the identified mutation is discussed. {\textcopyright} 2016 Wiley Periodicals, Inc.

}, keywords = {Abnormalities, Multiple, Base Sequence, Child, Preschool, Coloboma, DNA-Binding Proteins, Exome, Eyelid Neoplasms, Female, Frameshift Mutation, Genomic Imprinting, Humans, Lipoma, Pedigree}, issn = {1552-4833}, doi = {10.1002/ajmg.a.37683}, author = {Chac{\'o}n-Camacho, Oscar F and Sobreira, Nara and You, Jing and Pi{\~n}a-Aguilar, Raul E and Villegas-Ruiz, Vanessa and Zenteno, Juan C} } @article {62, title = {A Syndromic Intellectual Disability Disorder Caused by Variants in TELO2, a Gene Encoding a Component of the TTT Complex.}, journal = {Am J Hum Genet}, volume = {98}, year = {2016}, month = {2016 05 05}, pages = {909-918}, abstract = {

The proteins encoded by TELO2, TTI1, and TTI2 interact to form the TTT complex, a co-chaperone for maturation of the phosphatidylinositol 3-kinase-related protein kinases (PIKKs). Here we report six affected individuals from four families with intellectual disability (ID) and neurological and other congenital abnormalities associated with compound heterozygous variants in TELO2. Although their fibroblasts showed reduced steady-state levels of TELO2 and the other components of the TTT complex, PIKK functions were normal in cellular assays. Our results suggest that these TELO2 missense variants result in loss of function, perturb TTT complex stability, and cause an autosomal-recessive syndromic form of ID.

}, keywords = {Adolescent, Carrier Proteins, Child, Female, Humans, Intellectual Disability, Male, Molecular Chaperones, Pedigree, Phosphatidylinositol 3-Kinases, Protein-Serine-Threonine Kinases, Telomere-Binding Proteins}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2016.03.014}, author = {You, Jing and Sobreira, Nara L and Gable, Dustin L and Jurgens, Julie and Grange, Dorothy K and Belnap, Newell and Siniard, Ashley and Szelinger, Szabolcs and Schrauwen, Isabelle and Richholt, Ryan F and Vallee, Stephanie E and Dinulos, Mary Beth P and Valle, David and Armanios, Mary and Hoover-Fong, Julie} } @article {641, title = {An anadysplasia-like, spontaneously remitting spondylometaphyseal dysplasia secondary to lamin B receptor (LBR) gene mutations: further definition of the phenotypic heterogeneity of LBR-bone dysplasias.}, journal = {Am J Med Genet A}, volume = {167A}, year = {2015}, month = {2015 Jan}, pages = {159-63}, abstract = {

We describe a boy who has an anadysplasia-like spondylometaphyseal dysplasia. By whole exome sequencing he was shown to have compound heterozygous mutations of LBR that codes for the lamin B receptor. He shares many similarities with a case previously described, but in whom the early natural history could not be established [Borovik et al., 2013]. Thus, in addition to Greenberg dysplasia (a perinatal lethal disorder), homozygosity or compound heterozygosity of mutations in LBR can result in a mild, spontaneously regressing bone dysplasia.

}, keywords = {Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Mutation, Osteochondrodysplasias, Phenotype, Pregnancy, Radiography, Receptors, Cytoplasmic and Nuclear, Spine}, issn = {1552-4833}, doi = {10.1002/ajmg.a.36808}, author = {Sobreira, Nara and Modaff, Peggy and Steel, Gary and You, Jing and Nanda, Sonia and Hoover-Fong, Julie and Valle, David and Pauli, Richard M} } @article {146, title = {GeneMatcher aids in the identification of a new malformation syndrome with intellectual disability, unique facial dysmorphisms, and skeletal and connective tissue abnormalities caused by de novo variants in HNRNPK.}, journal = {Hum Mutat}, volume = {36}, year = {2015}, month = {2015 Oct}, pages = {1009-1014}, abstract = {

We report a new syndrome due to loss-of-function variants in the heterogeneous nuclear ribonucleoprotein K gene (HNRNPK). We describe two probands: one with a de novo frameshift (NM_002140.3: c.953+1dup), and the other with a de novo splice donor site variant (NM_002140.3: c.257G>A). Both probands have intellectual disability, a shared unique craniofacial phenotype, and connective tissue and skeletal abnormalities. The identification of this syndrome was made possible by a new online tool, GeneMatcher, which facilitates connections between clinicians and researchers based on shared interest in candidate genes. This report demonstrates that new Web-based approaches can be effective in helping investigators solve exome sequencing projects, and also highlights the newer paradigm of "reverse phenotyping," where characterization of syndromic features follows the identification of genetic variants.

}, keywords = {Abnormalities, Multiple, Adolescent, Child, Craniofacial Abnormalities, Databases, Genetic, Genetic Predisposition to Disease, Heterogeneous-Nuclear Ribonucleoprotein K, Humans, Information Dissemination, Intellectual Disability, Male, Muscular Atrophy, Phenotype, Polymorphism, Single Nucleotide, Ribonucleoproteins, Software, Web Browser}, issn = {1098-1004}, doi = {10.1002/humu.22837}, author = {Au, P Y Billie and You, Jing and Caluseriu, Oana and Schwartzentruber, Jeremy and Majewski, Jacek and Bernier, Francois P and Ferguson, Marcia and Valle, David and Parboosingh, Jillian S and Sobreira, Nara and Innes, A Micheil and Kline, Antonie D} } @article {191, title = {γ-Secretase Mutation in an African American Family With Hidradenitis Suppurativa.}, journal = {JAMA Dermatol}, volume = {151}, year = {2015}, month = {2015 Jun}, pages = {668-70}, keywords = {Adolescent, Adult, African Americans, Amyloid Precursor Protein Secretases, Exome, Female, Hidradenitis Suppurativa, Humans, Membrane Glycoproteins, Middle Aged, Mutation, Sequence Analysis, DNA, Young Adult}, issn = {2168-6084}, doi = {10.1001/jamadermatol.2014.5306}, author = {Chen, Sean and Mattei, Peter and You, Jing and Sobreira, Nara L and Hinds, Ginette A} }