X‐linked recessive Menkes disease: carrier detection in the case of a partial gene deletion

Poulsen, Louise K.; Horn, Nina; Møller, Lisbeth Birk

doi:10.1034/j.1399-0004.2002.620604.x

Cited by 15 publications

(11 citation statements)

References 27 publications

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“…In the coatis, no nail abnormalities were observed. Menkes kinky hair syndrome is a recessive disorder with hair shaft keratinization defects, but the accompanying neurological dysfunctions are a main feature and these were not present in coatis 9,10 . In hypotrichosis congenita of Marie Unna, there are irregular variations in hair shaft diameter with twisting and flattening, but in contrast to what we observed in coatis, follicles are reduced in number with chronicity 8,11 .…”

Section: Discussioncontrasting

confidence: 70%

“…In most of these syndromes, the underlying mechanism involves a defect in an important pathway in hair shaft keratinization. In hypotrichosis congenita of Marie Unna for example, a defect in the sulphur‐containing interfibrillar substance of the inner root sheath, cuticular cells and cortex of the hair is present, resulting in deficient binding of keratin fibrils 8,10–12 …”

Section: Discussionmentioning

confidence: 99%

“…In hypotrichosis congenita of Marie Unna for example, a defect in the sulphur-containing interfibrillar substance of the inner root sheath, cuticular cells and cortex of the hair is present, resulting in deficient binding of keratin fibrils. 8,[10][11][12] In dogs, several dysplastic diseases of the hair follicle are described. Because they are often breed-specific, they have a suspected hereditary basis.…”

Section: Discussionmentioning

confidence: 99%

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Congenital follicular dysplasia in five related coatimundis (Nasua nasua)

Nicolier

Welle

Walzer

et al. 2005

Veterinary Dermatology

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We report a congenital follicular dysplasia in five coatis from four different litters of the same parents born between 1996 and 2001. These coatis were born apparently alopecic with the entire body covered by very short dark hairs, with secondary lichenification of the skin, crusting and scaling. The main histopathological feature consisted of premature cornification of the cortical cells of the hair shaft. Cells were already fully cornified below the Adamson's fringe, leading to a disorganized, fragmented and constricted hair shaft. Based on the history of the animals and the nature of the lesions, a genetic defect in hair shaft keratinization was suspected.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Congenital follicular dysplasia in five related coatimundis (Nasua nasua)

Nicolier

Welle

Walzer

et al. 2005

Veterinary Dermatology

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“…Only if further information is needed about the consequence of the deletion at the protein level is RT‐PCR subsequently performed. Attempts to span the deletion is only performed if the MD patient has a large family with a number of potential female carriers, as spanning is the only one of the three methods that can be used for carrier detection (23). To date we have verified partial gene deletions in 55 unrelated MD patients covering the entire sequence using multiplex PCR (manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

X‐linked recessive Menkes disease: identification of partial gene deletions in affected males

et al. 2002

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Menkes disease is an X-linked recessive lethal disorder of copper metabolism, caused by defects in the ATP7A gene. Partial gene deletions comprise about 15% of the mutations causing Menkes disease. We have previously demonstrated identification of partial ATP7A deletions in patients by Southern blot analysis. In the present study, we report the use of three fast and reliable polymerase chain reaction (PCR)-based methods for the identification of partial ATP7A deletions in Menkes disease patients. First we demonstrate the use of multiplex PCR, a fast method for identification and rough localization of partial gene deletions, in which two exons of ATP7A are coamplified. Second, we present PCR amplification of genomic DNA across the deletion junctions, a method enabling identification of the deletion breakpoints and hence the exact size of the deletion. Finally, application of reverse transcription PCR (RT-PCR) for identification and localization of gene deletions at the cDNA level is demonstrated. By studying the mutation at the cDNA level the predicted effect of the mutation on the amino acid sequence and consequently the protein structure and function can be inferred. We demonstrate characterization of partial gene deletions in five patients, and in three of these we were able to determine the breakpoint sequences.

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“…The regions containing the polymorphic STR, CA repeat, G00-437-244 located in intron 5 [11], the SNP Rs2227291 located in exon 10 [12], and a SNP in intron 13 (c. 2782-29C > A) [12] respectively, were amplified by PCR in relevant patients. The region containing the CA repeat was amplified using the primer-pair; F: 5'gccaagtattatgaagcaagg-3'/R: 5'-taccagtcttgaccccaaaca-3'.…”

Section: Methodsmentioning

confidence: 99%

Exon duplications in the ATP7A gene: Frequency and Transcriptional Behaviour

Mogensen

Skjørringe

Kodama

et al. 2011

Orphanet J Rare Dis

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BackgroundMenkes 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.MethodsThe ATP7A gene was screened for exon duplications using multiplex ligation-dependent probe amplification (MLPA). The expression level of ATP7A was investigated by real-time PCR and detailed analysis of the ATP7A mRNA was performed by RT-PCR followed by sequencing. In order to investigate whether the identified duplicated fragments originated from a single or from two different X-chromosomes, polymorphic markers located in the duplicated fragments were analyzed.ResultsPartial ATP7A gene duplication was identified in 20 unrelated patients including one patient with Occipital Horn Syndrome (OHS). Duplications in the ATP7A gene are estimated from our material to be the disease causing mutation in 4% of the Menkes disease patients. The duplicated regions consist of between 2 and 15 exons. In at least one of the cases, the duplication was due to an intra-chromosomal event. Characterization of the ATP7A mRNA transcripts in 11 patients revealed that the duplications were organized in tandem, in a head to tail direction. The reading frame was disrupted in all 11 cases. Small amounts of wild-type transcript were found in all patients as a result of exon-skipping events occurring in the duplicated regions. In the OHS patient with a duplication of exon 3 and 4, the duplicated out-of-frame transcript coexists with an almost equally represented wild-type transcript, presumably leading to the milder phenotype.ConclusionsIn general, patients with duplication of only 2 exons exhibit a milder phenotype as compared to patients with duplication of more than 2 exons. This study provides insight into exon duplications in the ATP7A gene.

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X‐linked recessive Menkes disease: carrier detection in the case of a partial gene deletion

Cited by 15 publications

References 27 publications

Congenital follicular dysplasia in five related coatimundis (Nasua nasua)

Congenital follicular dysplasia in five related coatimundis (Nasua nasua)

X‐linked recessive Menkes disease: identification of partial gene deletions in affected males

Exon duplications in the ATP7A gene: Frequency and Transcriptional Behaviour

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