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PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome.
Eur J Hum Genet 2015; 23(12):1615-26EJ

Abstract

Array comparative genomic hybridization (aCGH) is a powerful genetic tool that has enabled the identification of novel imbalances in individuals with intellectual disability (ID), autistic disorders and congenital malformations. Here we report a 'genotype first' approach using aCGH on 13 unrelated patients with 19p13.3 submicroscopic rearrangement (11 deletions and 2 duplications) and review cases in the literature and in public databases. Shared phenotypic features suggest that these patients represent an interstitial microdeletion/microduplication syndrome at 19p13.3. Common features consist of abnormal head circumference in most patients (macrocephaly with the deletions and microcephaly with the duplications), ID with developmental delay (DD), hypotonia, speech delay and common dysmorphic features. The phenotype is associated with at least a ~0.113 Mb critical region harboring three strong candidate genes probably associated with DD, ID, speech delay and other dysmorphic features: MAP2K2, ZBTB7A and PIAS4, an E3 ubiquitin ligase involved in the ubiquitin signaling pathways, which we hypothesize for the first time to be associated with head size in humans.

Authors+Show Affiliations

Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.Signature Genomic Laboratories, PerkinElmer Inc., Spokane, WA, USA.Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.AI DuPont Hospital for Children, Wilmington, DE, USA.AI DuPont Hospital for Children, Wilmington, DE, USA.Hospital Vall D'Hebron, Barcelona, Spain.Hospital Vall D'Hebron, Barcelona, Spain.Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.Section of Clinical Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.Q-Genomics Laboratory, Barcelona, Spain.University of Louisville, Kentucky, USA.CGC-Genetics, Madrid, Spain.CGC-Genetics, Madrid, Spain.CGC-Genetics, Madrid, Spain.Hospital Quirón de Madrid, Madrid, Spain.Wake Forest University, Winston-Salem, NC, USA.Medical Genetics Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.The Children's Hospital of Philadelphia, Philadelphia, PA, USA.Hospital Saint Vincent de Paul, Lille, France.Ameripath Northeast, Shelton, CT, USA.Henry Ford Health System, Sterling Heights, Michigan, USA.Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.Section Cytogenetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.Section of Functional and Structural Genomics Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain. Section Cytogenetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.Kaiser Permanente, San Francisco, CA, USA.Center for Health and Biological Sciences, Pontifícia Universidade Católica do Paraná (PUC-PR), Curitiba, Brazil.Genetic Unit Hospital General de México, México, México. School of Medicine. Universidad Autónoma de México, México, México.Genetic Unit Hospital General de México, México, México.CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain. Section Cytogenetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain. Section of Clinical Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain. Section of Clinical Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25853300

Citation

Nevado, Julián, et al. "PIAS4 Is Associated With Macro/microcephaly in the Novel Interstitial 19p13.3 Microdeletion/microduplication Syndrome." European Journal of Human Genetics : EJHG, vol. 23, no. 12, 2015, pp. 1615-26.
Nevado J, Rosenfeld JA, Mena R, et al. PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome. Eur J Hum Genet. 2015;23(12):1615-26.
Nevado, J., Rosenfeld, J. A., Mena, R., Palomares-Bralo, M., Vallespín, E., Ángeles Mori, M., ... Lapunzina, P. (2015). PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome. European Journal of Human Genetics : EJHG, 23(12), pp. 1615-26. doi:10.1038/ejhg.2015.51.
Nevado J, et al. PIAS4 Is Associated With Macro/microcephaly in the Novel Interstitial 19p13.3 Microdeletion/microduplication Syndrome. Eur J Hum Genet. 2015;23(12):1615-26. PubMed PMID: 25853300.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome. AU - Nevado,Julián, AU - Rosenfeld,Jill A, AU - Mena,Rocío, AU - Palomares-Bralo,María, AU - Vallespín,Elena, AU - Ángeles Mori,María, AU - Tenorio,Jair A, AU - Gripp,Karen W, AU - Denenberg,Elizabeth, AU - Del Campo,Miguel, AU - Plaja,Alberto, AU - Martín-Arenas,Rubén, AU - Santos-Simarro,Fernando, AU - Armengol,Lluis, AU - Gowans,Gordon, AU - Orera,María, AU - Sanchez-Hombre,M Carmen, AU - Corbacho-Fernández,Esther, AU - Fernández-Jaén,Alberto, AU - Haldeman-Englert,Chad, AU - Saitta,Sulagna, AU - Dubbs,Holly, AU - Bénédicte,Duban B, AU - Li,Xia, AU - Devaney,Lani, AU - Dinulos,Mary Beth, AU - Vallee,Stephanie, AU - Crespo,M Carmen, AU - Fernández,Blanca, AU - Fernández-Montaño,Victoria E, AU - Rueda-Arenas,Inmaculada, AU - de Torres,María Luisa, AU - Ellison,Jay W, AU - Raskin,Salmo, AU - Venegas-Vega,Carlos A, AU - Fernández-Ramírez,Fernando, AU - Delicado,Alicia, AU - García-Miñaúr,Sixto, AU - Lapunzina,Pablo, Y1 - 2015/04/08/ PY - 2014/10/12/received PY - 2014/12/23/revised PY - 2015/02/17/accepted PY - 2015/4/9/entrez PY - 2015/4/9/pubmed PY - 2016/8/25/medline SP - 1615 EP - 26 JF - European journal of human genetics : EJHG JO - Eur. J. Hum. Genet. VL - 23 IS - 12 N2 - Array comparative genomic hybridization (aCGH) is a powerful genetic tool that has enabled the identification of novel imbalances in individuals with intellectual disability (ID), autistic disorders and congenital malformations. Here we report a 'genotype first' approach using aCGH on 13 unrelated patients with 19p13.3 submicroscopic rearrangement (11 deletions and 2 duplications) and review cases in the literature and in public databases. Shared phenotypic features suggest that these patients represent an interstitial microdeletion/microduplication syndrome at 19p13.3. Common features consist of abnormal head circumference in most patients (macrocephaly with the deletions and microcephaly with the duplications), ID with developmental delay (DD), hypotonia, speech delay and common dysmorphic features. The phenotype is associated with at least a ~0.113 Mb critical region harboring three strong candidate genes probably associated with DD, ID, speech delay and other dysmorphic features: MAP2K2, ZBTB7A and PIAS4, an E3 ubiquitin ligase involved in the ubiquitin signaling pathways, which we hypothesize for the first time to be associated with head size in humans. SN - 1476-5438 UR - https://www.unboundmedicine.com/medline/citation/25853300/PIAS4_is_associated_with_macro/microcephaly_in_the_novel_interstitial_19p13_3_microdeletion/microduplication_syndrome_ L2 - http://dx.doi.org/10.1038/ejhg.2015.51 DB - PRIME DP - Unbound Medicine ER -