caa a22 4500 445860952 CHVBK 20180317145442.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00439-011-0968-y doi (NATIONALLICENCE)springer-10.1007/s00439-011-0968-y BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome [Elektronische Daten] [Linda Reis, Rebecca Tyler, Kala Schilter, Omar Abdul-Rahman, Jeffrey Innis, Beth Kozel, Adele Schneider, Tanya Bardakjian, Edward Lose, Donna Martin, Ulrich Broeckel, Elena Semina] BMP4 loss-of-function mutations and deletions have been shown to be associated with ocular, digital, and brain anomalies, but due to the paucity of these reports, the full phenotypic spectrum of human BMP4 mutations is not clear. We screened 133 patients with a variety of ocular disorders for BMP4 coding region mutations or genomic deletions. BMP4 deletions were detected in two patients: a patient affected with SHORT syndrome and a patient with anterior segment anomalies along with craniofacial dysmorphism and cognitive impairment. In addition to this, three intragenic BMP4 mutations were identified. A patient with anophthalmia, microphthalmia with sclerocornea, right-sided diaphragmatic hernia, and hydrocephalus was found to have a c.592C>T (p.R198X) nonsense mutation in BMP4. A frameshift mutation, c.171dupC (p.E58RfsX17), was identified in two half-siblings with anophthalmia/microphthalmia, discordant developmental delay/postaxial polydactyly, and poor growth as well as their unaffected mother; one affected sibling carried an additional BMP4 mutation in the second allele, c.362A>G (p.H121R). This is the first report indicating a role for BMP4 in SHORT syndrome, Axenfeld-Rieger malformation, growth delay, macrocephaly, and diaphragmatic hernia. These results significantly expand the number of reported loss-of-function mutations, further support the critical role of BMP4 in ocular development, and provide additional evidence of variable expression/non-penetrance of BMP4 mutations. The Author(s), 2011 Reis Linda Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut Tyler Rebecca Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut Schilter Kala Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut Abdul-Rahman Omar Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA aut Innis Jeffrey Department of Pediatrics and Human Genetics, The University of Michigan Medical Center, Ann Arbor, MI, USA aut Kozel Beth Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA aut Schneider Adele Division of Genetics, Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, PA, USA aut Bardakjian Tanya Division of Genetics, Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, PA, USA aut Lose Edward Department of Clinical Genetics, University of Alabama, Birmingham, AL, USA aut Martin Donna Department of Pediatrics and Human Genetics, The University of Michigan Medical Center, Ann Arbor, MI, USA aut Broeckel Ulrich Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut Semina Elena Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut Human Genetics Springer-Verlag 130/4(2011-10-01), 495-504 0340-6717 130:4<495 2011 130 439 https://doi.org/10.1007/s00439-011-0968-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0968-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Reis Linda Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Tyler Rebecca Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Schilter Kala Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Abdul-Rahman Omar Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA aut NATIONALLICENCE 700 1- Innis Jeffrey Department of Pediatrics and Human Genetics, The University of Michigan Medical Center, Ann Arbor, MI, USA aut NATIONALLICENCE 700 1- Kozel Beth Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA aut NATIONALLICENCE 700 1- Schneider Adele Division of Genetics, Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Bardakjian Tanya Division of Genetics, Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Lose Edward Department of Clinical Genetics, University of Alabama, Birmingham, AL, USA aut NATIONALLICENCE 700 1- Martin Donna Department of Pediatrics and Human Genetics, The University of Michigan Medical Center, Ann Arbor, MI, USA aut NATIONALLICENCE 700 1- Broeckel Ulrich Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Semina Elena Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/4(2011-10-01), 495-504 0340-6717 130:4<495 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer