Occipital Horn Syndrome as a Result of Splice Site Mutations in ATP7A. No Activity of ATP7A Splice Variants Missing Exon 10 or Exon 15

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Splice Site Mutations in the ATP7A Gene

Menkes disease (MD) is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12 mutations for their effect on the mRNA transcript in vivo. Transcriptional data from another 16 mut...

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Constitutive skipping of alternatively spliced exon 10 in the ATP7A gene abolishes Golgi localization of the menkes protein and produces the occipital horn syndrome.

The ATP7A gene encodes a copper-transporting ATPase. Mutations in this gene result in two clinically distinct X-linked inherited disorders: Menkes disease and occipital horn syndrome (OHS). We identified a single exon skipping in the ATP7A transcript in cells from the affected proband, affected cousins and obligate carriers in a family with OHS. Genomic sequencing identified an A-->T transversi...

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Exon duplications in the ATP7A gene: Frequency and Transcriptional Behaviour

BACKGROUND Menkes disease (MD) is an X-linked, fatal neurodegenerative disorder of copper metabolism, caused by mutations in the ATP7A gene. Thirty-three Menkes patients in whom no mutation had been detected with standard diagnostic tools were screened for exon duplications in the ATP7A gene. METHODS The ATP7A gene was screened for exon duplications using multiplex ligation-dependent probe am...

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A novel nonsense ATP7A pathogenic variant in a family exhibiting a variable occipital horn syndrome phenotype

We report on a family with occipital horn syndrome (OHS) diagnosed in the proband's late fifties. A novel ATP7A pathogenic variant (c.4222A > T, p.(Lys1408*)), representing the first nonsense variant and the second late truncation causing OHS rather than classic Menkes disease, was found to segregate in the family. The predicted maintenance of transmembrane domains is consistent with a residual...

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ژورنال

عنوان ژورنال: Frontiers in Molecular Neuroscience

سال: 2021

ISSN: 1662-5099

DOI: 10.3389/fnmol.2021.532291