ArticleClinical genetics2011
Favorably skewed X-inactivation accounts for neurological sparing in female carriers of Menkes disease.
Article in Clinical genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00001262 (Early Copper Histidine Therapy in Menkes Disease), which is not on this map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Early Copper Histidine Therapy in Menkes Disease
Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2014Trial
- From inactivation to intervention: X chromosome silencing in disease pathogenesis and emerging therapeutic strategies.Genes & diseases · 2026Review
- Disorders Mimicking Wilson's Disease: Clinical, Biochemical, and Molecular Perspectives for Accurate Differential Diagnosis.Diagnostics (Basel, Switzerland) · 2026Review
- Relationship between Glucose-6-Phosphate Dehydrogenase Deficiency, X-Chromosome Inactivation and Inflammatory Markers.Antioxidants (Basel, Switzerland) · 2023Article
- Article
- Dosage Compensation in Females with X-Linked Metabolic Disorders.International journal of molecular sciences · 2021Review
- Novel familial IQSEC2 pathogenic sequence variant associated with neurodevelopmental disorders and epilepsy.Neurogenetics · 2020Article
- Mosaicism in Cutaneous Disorders.Annual review of genetics · 2017Review
- Genetics of Hereditary Ataxia in Scottish Terriers.Journal of veterinary internal medicine · 2017Article
- A sibship with duplication of Xq28 inherited from the mother; genomic characterization and clinical outcomes.BMC medical genetics · 2017Article
- The Role of X-Chromosome Inactivation in Retinal Development and Disease.Advances in experimental medicine and biology · 2016Article
- Menkes disease: what a multidisciplinary approach can do.Journal of multidisciplinary healthcare · 2016Review
- Menkes disease with discordant phenotype in female monozygotic twins.American journal of medical genetics. Part A · 2015Article
- The human sex ratio from conception to birth.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Incontinentia pigmenti: report on data from 2000 to 2013.Orphanet journal of rare diseases · 2014Article
- Characterization of X chromosome inactivation using integrated analysis of whole-exome and mRNA sequencing.PloS one · 2014Article
- Clinical expression of Menkes disease in females with normal karyotype.Orphanet journal of rare diseases · 2012Article
- Molecular correlates of epilepsy in early diagnosed and treated Menkes disease.Journal of inherited metabolic disease · 2010Article
- Menkes disease and response to copper histidine: An Indian case series.Annals of Indian Academy of NeurologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Classical Menkes disease is an X-linked recessive neurodegenerative disorder caused by mutations in ATP7A, which is located at Xq13.1-q21. ATP7A encodes a copper-transporting P-type ATPase and plays a critical role in development of the central nervous system. With rare exceptions involving sex chromosome aneuploidy or X-autosome translocations, female carriers of ATP7A mutations are asymptomatic except for subtle hair and skin abnormalities, although the mechanism for this neurological sparing has not been reported. We studied a three-generation family in which a severe ATP7A mutation, a 5.5-kb genomic deletion spanning exons 13 and 14, segregated. The deletion junction fragment was amplified from the proband by long-range polymerase chain reaction and sequenced to characterize the breakpoints. We screened at-risk females in the family for this junction fragment and analyzed their X-inactivation patterns using the human androgen-receptor (HUMARA) gene methylation assay. We detected the junction fragment in the proband, two obligate heterozygotes, and four of six at-risk females. Skewed inactivation of the X chromosome harboring the deletion was noted in all female carriers of the deletion (n = 6), whereas random X-inactivation was observed in all non-carriers (n = 2). Our results formally document one mechanism for neurological sparing in female carriers of ATP7A mutations. Based on review of X-inactivation patterns in female carriers of other X-linked recessive diseases, our findings imply that substantial expression of a mutant ATP7A at the expense of the normal allele could be associated with neurologic symptoms in female carriers of Menkes disease and its allelic variants, occipital horn syndrome, and ATP7A-related distal motor neuropathy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.