title: Disturbed copper transport in humans. Part 1: mutations of the ATP7A gene lead to Menkes disease and occipital horn syndrome.
abstract: Mutations of the ATP7A gene (OMIM 300011) lead to the Menkes disease (MD, OMIM 309400) involving impaired brain development, neurological degeneration, connective tissue abnormalities, and high lethality in early infancy. Occipital horn syndrome (OHS, OMIM 304150), a milder phenotype, is also caused by ATP7A gene mutations. In MD patients, an early copper-histidine treatment may prevent the neurological impairment and prolong survival leading to an OHS phenotype. To demonstrate the genotype/phenotype correlation, two male patients are reported with different ATP7A gene mutations and several phenotypes. In the first patient with the MD phenotype, a mutation within the exon 20 (Gln1288Ter) was found producing a stop codon just prior to the highly conserved ATP binding domain. The OHS phenotype of the second patient was caused by a splice site mutation involving the position +6 of intron 6 within a copper binding domain. Small amounts of correctly spliced ATP7A transcript were sufficient to develop the milder OHS phenotype in this patient (OMIM 30001.0006). In conclusion, mutations of the copper transporting P-type ATPase ATP7A gene cause distinct human diseases showing some genotype/phenotype correlation and implications for treatment.
authors.affiliation: Department of Pediatrics, Friedrich-Schiller University of Jena, Germany. joerg.seidel@med.uni-jena.de
authors.forename: J
authors.initials: J
authors.lastname: Seidel
authors.forename: L B
authors.initials: LB
authors.lastname: Møller
authors.forename: H J
authors.initials: HJ
authors.lastname: Mentzel
authors.forename: E
authors.initials: E
authors.lastname: Kauf
authors.forename: S
authors.initials: S
authors.lastname: Vogt
authors.forename: S
authors.initials: S
authors.lastname: Patzer
authors.forename: U
authors.initials: U
authors.lastname: Wollina
authors.forename: F
authors.initials: F
authors.lastname: Zintl
authors.forename: N
authors.initials: N
authors.lastname: Horn
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002675:Child, Preschool; D018388:Codon, Terminator / Q000235:genetics; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D004535:Ehlers-Danlos Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005091:Exons; D005838:Genotype; D006197:Hair / Q000473:pathology; D006801:Humans; D007438:Introns; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D012326:RNA Splicing; D011993:Recombinant Fusion Proteins; D012886:Skull / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D018388:Codon, Terminator; D011993:Recombinant Fusion Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases