Media type: E-Article Title: A novel inverted 17p13.3 microduplication disrupting PAFAH1B1 (LIS1) in a girl with syndromic lissencephaly Contributor: Classen, Sabrina; Goecke, Timm; Drechsler, Matthias; Betz, Beate; Nickel, Natalie; Beier, Manfred; Schaper, Jörg; Karenfort, Michael; Royer‐Pokora, Brigitte imprint: Wiley, 2013 Published in: American Journal of Medical Genetics Part A Language: English DOI: 10.1002/ajmg.a.35904 ISSN: 1552-4825; 1552-4833 Keywords: Genetics (clinical) ; Genetics Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>We describe a female patient with mild lissencephaly (pachygyria), severe intellectual disability, and facial dysmorphisms with an inverted 1.4 Mb microduplication of chromosome 17p13.3. The 17p13.3 microduplication syndrome is associated with mild intellectual disabiltiy and contains, among others, the <jats:italic>PAFAH1B1</jats:italic> (<jats:italic>LIS1</jats:italic>) gene, whereas microdeletions of the same segment cause Miller–Dieker syndrome (MDS) with severe to profound retardation. The duplication identified in our patient encompasses 29 genes, including <jats:italic>CRK</jats:italic> and <jats:italic>YWHAE</jats:italic>. The proximal breakpoint of the duplication is located in the first intron of the <jats:italic>PAFAH1B1</jats:italic> gene. Analysis of total RNA showed that only one <jats:italic>PAFAH1B1</jats:italic> allele is expressed. Therefore, this patient has a unique alteration: a duplication including <jats:italic>YWHAE</jats:italic> and <jats:italic>CRK</jats:italic> and haploinsufficiency of <jats:italic>PAFAH1B1</jats:italic>. Overexpression of <jats:italic>YWHAE</jats:italic> is associated with macrosomia, mild developmental delay, autism and facial dysmorphisms, and deletion of <jats:italic>PAFAH1B1</jats:italic> alone leads to isolated lissencephaly (ILS). The patient described here shares features with MDS, but she is affected to a lesser degree. Her facial features are similar to MDS, and she has manifestations seen in other cases with <jats:italic>YWHAE</jats:italic> duplication. © 2013 Wiley Periodicals, Inc.</jats:p></jats:sec>