Clin Genet 2001: 60: 421–430 Printed in Ireland. All rights resered Original Article A family with a grand-maternally derived interstitial duplication of proximal 15q Boyar FZ, Whitney MM, Lossie AC, Gray BA, Keller KL, Stalker HJ, Zori RT, Geffken G, Mutch J, Edge PJ, Voeller KS, Williams CA, Driscoll DJ. A family with a grand-maternally derived interstitial dupli- cation of proximal 15q. Clin. Genet. 2001: 60: 421–430. © Munksgaard, 2001 About 1% of individuals with autism or types of pervasive developmen- tal disorder have a duplication of the 15q11-q13 region. These abnor- malities can be detected by routine G-banded chromosome study, showing an extra marker chromosome, or demonstrated by fluorescence in situ hybridization (FISH) analysis, revealing an interstitial duplica- tion. We report here the molecular, cytogenetic, clinical and neuropsy- chiatric evaluations of a family in whom 3 of 4 siblings inherited an interstitial duplication of 15q11-q13. This duplication was inherited from their mother who also had a maternally derived duplication. Af- fected family members had apraxia of speech, phonological awareness deficits, developmental language disorder, dyslexia, as well as limb apraxia but did not have any dysmorphic clinical features. The obser- vations in this family suggest that the phenotypic manifestations of proximal 15q duplications may also involve language-based learning disabilities. FZ Boyar a , MM Whitney a , AC Lossie a , BA Gray a , KL Keller a , HJ Stalker a , RT Zori a , G Geffken c , J Mutch c , PJ Edge c , KS Voeller b , CA Williams a and DJ Driscoll a a Raymond C. Philips Unit, Division of Pediatric Genetics, Department of Pediatrics and Center for Mammalian Genetics, University of Florida College of Medicine, b Greenwood Genetic Center, Greenwood, SC, c Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL, USA Key words: Angelman – apraxia of speech – autism – chromosome 15 – dyslexia – imprinting – interstitial duplication – phonological awareness deficit Corresponding authors: DJ Driscoll, Ph.D., MD, and CA Williams, MD, Pediatric Genet- ics, Box 100296, University of Florida Col- lege of Medicine, Gainesville, FL 32610-0296, USA. Tel.: +1 352 3924104; fax: +1 352 3923051; e-mail: driscdj@peds.ufl.edu; willica@peds.ufl.edu Received 19 June 2001, revised and ac- cepted for publication 30 August 2001 Chromosome region 15q11-q13 is prone to genetic rearrangements, often leading to visible chromoso- mal abnormalities, such as marker chromosomes. Chiasmata frequency is increased in the 15q11-q13 area (1) and recent findings suggest that duplicated genes may account for this phenomenon. A large non-processed duplication of the novel gene HERC2 is located within the common proximal and distal microdeletion breakpoints (2) for the Angelman (AS) and Prader – Willi syndromes (PWS) (3). In addition, the most centromeric eu- chromatic region in 15q11 contains several non- processed (pseudogene) duplications, including the neurofibromatosis type 1 gene (NF1), the im- munoglobin heavy chain (IgH) D segment gene and the gamma amino butyric acid receptor -5 gene, GABRA5 (4–6). Microdeletions of chromosome 15q11-q13 re- gion result in various phenotypes, the best known being the imprinted disorders of AS and PWS (7 – 9). Alternatively, interstitial microduplications of 15q11-q13 (referred hereafter as dup(15)) are associated with a wide variety of behaviors, includ- ing those observed in autism and autism spectrum disorders (10 – 12). However, physical dysmorphic traits are usually not observed (13). Until recently, dup(15)s have been considered relatively rare, al- though 15q11-q13 duplications present in marker chromosomes have been well described for several decades, and are the most common supernumerary 421