The Xq22 inversion breakpoint interrupted a novel Ras-like GTPase gene in a patient with Duchenne muscular dystrophy and profound mental retardation

Am J Hum Genet. 2002 Sep;71(3):637-45. doi: 10.1086/342208. Epub 2002 Jul 23.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Chromosome Breakage / genetics*
  • Chromosome Inversion*
  • Female
  • Humans
  • Intellectual Disability / complications
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Mitochondria / chemistry
  • Mitochondrial Proteins / analysis
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics*
  • Molecular Sequence Data
  • Muscular Dystrophy, Duchenne / complications*
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / pathology
  • Protein Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transfection
  • X Chromosome / genetics*
  • ras Proteins / analysis
  • ras Proteins / chemistry
  • ras Proteins / genetics*


  • Mitochondrial Proteins
  • RNA, Messenger
  • RAB40AL protein, human
  • ras Proteins

Associated data

  • GENBANK/Z95624
  • OMIM/229300
  • OMIM/277900
  • OMIM/300075
  • OMIM/300127
  • OMIM/300142
  • OMIM/300377
  • OMIM/312080
  • OMIM/602783
  • RefSeq/NT_027217