title: The Xq22 inversion breakpoint interrupted a novel Ras-like GTPase gene in a patient with Duchenne muscular dystrophy and profound mental retardation.
abstract: A male patient with profound mental retardation, athetosis, nystagmus, and severe congenital hypotonia (Duchenne muscular dystrophy [DMD]) was previously shown to carry a pericentric inversion of the X chromosome, 46,Y,inv(X)(p21.2q22.2). His mother carried this inversion on one X allele. The patient's condition was originally misdiagnosed as cerebral palsy, and only later was it diagnosed as DMD. Because the DMD gene is located at Xp21.2, which is one breakpoint of the inv(X), and because its defects are rarely associated with severe mental retardation, the other clinical features of this patient were deemed likely to be associated with the opposite breakpoint at Xq22. Our precise molecular-cytogenetic characterization of both breakpoints revealed three catastrophic genetic events that had probably influenced neuromuscular and cognitive development: deletion of part of the DMD gene at Xp21.2, duplication of the human proteolipid protein gene (PLP) at Xq22.2, and disruption of a novel gene. The latter sequence, showing a high degree of homology to the Sec4 gene of yeast, encoded a putative small guanine-protein, Ras-like GTPase that we have termed "RLGP." Immunocytochemistry located RLGP at mitochondria. We speculate that disruption of RLGP was responsible for the patient's profound mental retardation.
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Saito-Ohara
authors.forename: Yoji
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Kishan Lal
authors.initials: KL
authors.lastname: Agarwala
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hayashi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D019457:Chromosome Breakage / Q000235:genetics*; D007446:Chromosome Inversion; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000737:chemistry; D024101:Mitochondrial Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D020388:Muscular Dystrophy, Duchenne / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014960:X Chromosome / Q000235:genetics*; D018631:ras Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C466300:RAB40AL protein, human; D018631:ras Proteins