Deletions in chromosome 6p22.3-p24.3, including ATXN1, are associated with developmental delay and autism spectrum disorders

Celestino-Soper, Skinner Cindy, Schroer Richard, Eng Patricia, Shenai Jayant, Nowaczyk, Terespolsky Deborah, Cushing Donna, Patel, Immken Ladonna, Willis Alecia, Wiszniewska Joanna, Matalon Reuben, Rosenfeld, Stevenson, Kang, Cheung Sau, Beaudet, Stankiewicz Pawel

Description

Interstitial deletions of the short arm of chromosome 6 are rare and have been associated with developmental delay, hypotonia, congenital anomalies, and dysmorphic features. We used array comparative genomic hybridization in a South Carolina Autism Project (SCAP) cohort of 97 subjects with autism spectrum disorders (ASDs) and identified an ~ 5.4 Mb deletion on chromosome 6p22.3-p23 in a 15-year-old patient with intellectual disability and ASDs. Subsequent database queries revealed five additional individuals with overlapping submicroscopic deletions and presenting with developmental and speech delay, seizures, behavioral abnormalities, heart defects, and dysmorphic features. The deletion found in the SCAP patient harbors ATXN1 , DTNBP1 , JARID2 , and NHLRC1 that we propose may be responsible for ASDs and developmental delay.

Sujets

• Array comparative genomic hybridization

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 49
• Langue: English

Extrait

Celestino-Soper et al . Molecular Cytogenetics 2012, 5 :17 http://www.molecularcytogenetics.org/content/5/1/17

R E S E A R C H Open Access Deletions in chromosome 6p22.3-p24.3, including ATXN1 , are associated with developmental delay and autism spectrum disorders Patrícia BS Celestino-Soper 1 , Cindy Skinner 2 , Richard Schroer 2 , Patricia Eng 1 , Jayant Shenai 3 , Malgorzata MJ Nowaczyk 4 , Deborah Terespolsky 5 , Donna Cushing 5 , Gayle S Patel 6 , LaDonna Immken 6 , Alecia Willis 1 , Joanna Wiszniewska 1 , Reuben Matalon 7 , Jill A Rosenfeld 8 , Roger E Stevenson 2 , Sung-Hae L Kang 1 , Sau Wai Cheung 1 , Arthur L Beaudet 1 and Pawel Stankiewicz 1*

Abstract Interstitial deletions of the short arm of chromosome 6 are rare and have been associated with developmental delay, hypotonia, congenital anomalies, and dysmorphic features. We used array comparative genomic hybridization in a South Carolina Autism Project (SCAP) cohort of 97 subjects with autism spectrum disorders (ASDs) and identified an ~ 5.4 Mb deletion on chromosome 6p22.3-p23 in a 15-year-old patient with intellectual disability and ASDs. Subsequent database queries revealed five additional individuals with overlapping submicroscopic deletions and presenting with developmental and speech delay, seizures, behavioral abnormalities, heart defects, and dysmorphic features. The deletion found in the SCAP patient harbors ATXN1 , DTNBP1 , JARID2 , and NHLRC1 that we propose may be responsible for ASDs and developmental delay. Keywords: 6p deletions, Copy-number variants, Array comparative genomic hybridization

Background psychomotor and growth delay, hypotonia as well as sev- Deletions involving the distal part of the short arm of  eral congenital abnormalitie s, including hydrocephalus, chromosome 6 are relatively rare. Terminal deletions of microcephaly, structural eye abnormalities, hypertelorism, 6p24-pter have been associated with developmental  low set and rotated ears, nasal anomalies, micrognathia, delay, brain malformations (including Dandy-Walker palatal abnormalities, short folded neck, defects of heart, malformation), anterior eye chamber abnormalities, kidney, and feet, abnormal genitalia, and abnormal fingers hearing loss, ear abnormalitie s, micrognathia, and heart with hypoplastic nails [4,5,13,22-26]. defects [1-6]. Patients with larger sized deletions of  Here, we describe six individuals, five of whom have 6p23-pter also presented with microcephaly, genital overlapping interstitial deletions in chromosome 6p22.3- anomalies, language impairment, and delayed motor  p24.3 encompassing ATXN1 . The majority of patients development [1,3,5,7-14]. The identified ocular develop- had neurological or behavioral abnormalities, including mental abnormalities are caused by deficiency of the developmental and speech delay, autism spectrum disor- dosage sensitive FOXC1 gene (MIM 01090) [15-20]. In  ders (ASDs), attention deficit hyperactivity disorder addition, deletions and d uplications involving FOXC1 (ADHD), repetitive behaviors, and various dysmorphic have been shown recently to be responsible for Dandy- features. Walker malformation [21]. Interstitial deletions of 6p22-p24 have been reported Clinical reports even less often and are generally associated with Patient 1 This 15-year-old male proband was enrolled in the South * Correspondence: [e-mail] Carolina Autism Project (SCAP) study at the J.C. Self 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Research Institute of Human Genetics at the Greenwood Houston, TX, USA Full list of author information is available at the end of the article Genetics Center in Greenwood, South Carolina. He was © 2012 Celestino-Soper et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.