title: 7p22.1 microdeletions involving ACTB associated with developmental delay, short stature, and microcephaly.
abstract: There are no published reports of patients harboring microdeletions involving the 7p22.1 region. Although 7p22.1 microdeletions are rare, some reports have shown microduplications encompassing this region. In this study, we report five patients with overlapping deletions of the 7p22.1 region. The patients exhibited clinical similarities including non-specific developmental delay, short stature, microcephaly, and other distinctive features. The shortest region of overlap within the 7p22.1 region includes five genes, FBXL18, ACTB, FSCN1, RNF216, and ZNF815P. Of these genes, only ACTB is known to be associated with an autosomal dominant trait. Dominant negative mutations in ACTB are responsible for Baraitser-Winter syndrome 1. We analyzed ACTB expression in immortalized lymphocytes derived from one of the patients and found that it was reduced to approximately half that observed in controls. This indicates that ACTB expression is linearly correlated with the gene copy number. We suggest that haploinsufficiency of ACTB may be responsible for the clinical features of patients with 7p22.1 microdeletions.
authors.affiliation: Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan; Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Department of Pediatrics, Tottori Prefectural Central Hospital, Tottori, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Narai
authors.affiliation: Department of Pediatrics, Tottori Prefectural Central Hospital, Tottori, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Togawa
authors.affiliation: Department of Pediatrics, Tottori Prefectural Central Hospital, Tottori, Japan.
authors.forename: Tomotsune
authors.initials: T
authors.lastname: Doumoto
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sangu
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Vanakker
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: de Paepe
authors.affiliation: Department of Paediatrics, School of Medicine, University of Western Sydney, New South Wales, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Department of Paediatrics, School of Medicine, University of Western Sydney, New South Wales, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Whitehall
authors.affiliation: Centre for Genetic Education, University of Sydney, New South Wales, Australia.
authors.forename: Sally
authors.initials: S
authors.lastname: Brescianini
authors.affiliation: CHU Lille, Hopital Jeanne de Flandre, Service de Genetique Clinique, F-59000 Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Petit
authors.affiliation: CHU Lille, Hopital Jeanne de Flandre, Laboratoire de Genetique Medicale, F-59000 Lille, France.
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000503:physiopathology; D000199:Actins / Q000096:biosynthesis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D004392:Dwarfism / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype
chemical_list: D000199:Actins
keywords: 7p22.1 microdeletion; Baraitser-Winter syndrome 1 (BRWS1); Developmental delay; Microcephaly; Short stature; The beta-actin gene (ACTB)