title: Axonal neuropathy with unusual pattern of amyotrophy and alacrima associated with a novel AAAS mutation p.Leu430Phe.
abstract: The triple A syndrome is caused by autosomal recessively inherited mutations in the AAAS gene and is characterized by achalasia, alacrima and adrenal insufficiency as well as progressive neurological impairment. We report on a 14-year-old girl with slowly progressive axonal motor neuropathy with conspicuous muscle wasting of hypothenars and calves as well as alacrima. The mutation analysis of the AAAS gene revealed a compound heterozygous mutation: a c.251G>A mutation in exon 2 that had been reported previously, and a novel c.1288C>T mutation in exon 14. At the transcriptional level, the c.251G>A transition results in an aberrant splicing and decay of this RNA strand so that the particular clinical picture results from the novel c.1288C>T, (p.Leu430Phe, L430F) mutation in a hemizygous form. With transfection experiments, we demonstrate that GFP-ALADIN(L430F) correctly localizes to nuclear pore complexes. Therefore, we conclude that this point mutation impairs ALADIN function at the nuclear pore.
authors.affiliation: Children's Hospital, Technical University Dresden, Dresden, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Koehler
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
authors.forename: Manuela
authors.initials: M
authors.lastname: Krumbholz
authors.forename: Barbara
authors.initials: B
authors.lastname: Kind
authors.forename: Carsten
authors.initials: C
authors.lastname: Bönnemann
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D004252:DNA Mutational Analysis; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007766:Lacrimal Apparatus Diseases / Q000150:complications / Q000235:genetics*; D007930:Leucine / Q000235:genetics; D009133:Muscular Atrophy / Q000150:complications / Q000235:genetics*; D009139:Musculoskeletal Abnormalities / Q000150:complications / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics*; D010649:Phenylalanine / Q000235:genetics; D017354:Point Mutation; D013577:Syndrome; D014162:Transfection
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D010649:Phenylalanine; D007930:Leucine