A new X linked recessive deafness syndrome with blindness, dystonia, fractures, and mental deficiency is linked to Xq22.

Tranebjærg, Lisbeth; Schwartz, Charles E.; Eriksen, H; Andréasson, Sten; Ponjavic, Vesna; Dahl, Andy; Stevenson, Roger E.; May, Melanie; Arena, Fernando; Barker, David F.

doi:10.1136/jmg.32.4.257

Cited by 168 publications

(118 citation statements)

References 36 publications

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…However, these signal tags may not function in mitochondrial diseased cells. For example, the signal tags could not be used to correct defects in the mitochondrial protein import [34] of their cargo. Similarly, signal tags may be of little benefit in the case of mtDNA-encoded-proteins, as these proteins are generally too hydrophobic to maintain the unfolded conformation that is required for signal tag-mediated import [35].…”

Section: Discussionmentioning

confidence: 99%

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

Yasuzaki

Yamada

Kanefuji

et al. 2013

Journal of Controlled Release

View full text Add to dashboard Cite

ABSTRACT.Mitochondrial genetic disorders are a major cause of mitochondrial diseases. It is therefore likely that mitochondrial gene therapy will be useful for the treatment of such diseases. Here, we report on the possibility of mitochondrial gene delivery in skeletal muscle using hydrodynamic limb vein (HLV) injection. The HLV injection procedure, a useful method for transgene expression in skeletal muscle, involves the rapid injection of a large volume of naked plasmid DNA (pDNA) into the distal vein of a limb. We hypothesized that the technique could be used to deliver pDNA not only to nuclei but also mitochondria, since cytosolic pDNA that is internalized by the method may be able to overcome mitochondrial membrane. We determined if pDNA could be delivered to myofibrillar mitochondria by HLV injection by PCR analysis. Mitochondrial toxicity assays showed that the HLV injection had no influence on mitochondrial function. These findings indicate that HLV injection promises to be a useful technique for in vivo mitochondrial gene delivery.

show abstract

Section: Discussionmentioning

confidence: 99%

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

Yasuzaki

Yamada

Kanefuji

et al. 2013

Journal of Controlled Release

View full text Add to dashboard Cite

show abstract

“…[1][2][3] In 1996, the DDP gene was characterised and disease-causing mutations were reported in the original Norwegian and two other families. 4 The DDP cDNA sequence is 1167 bp in length excluding the poly(A) + tail.…”

Section: Introductionmentioning

confidence: 99%

A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness–dystonia–optic atrophy syndrome

et al. 2000

View full text Add to dashboard Cite

We report the first de novo mutation in the DDP gene in a Dutch 11-year-old boy with deafness and dystonia. Previously reported mutations in the DDP gene have all been frameshifts/nonsense mutations or deletion of the entire gene as part of a larger deletion encompassing the BTK gene. The clinical presentation was uniformly characterised by sensorineural hearing loss, dystonia, mental deterioration, paranoid psychotic features, and optic atrophy, indicating progressive neurodegeneration. Our report illustrates that de novo mutations occur and that a missense mutation, C66W, may cause an equally severe clinical picture. The diagnosis of sensorineural hearing impairment associated with neurologic and visual disability in a male, therefore, should encourage the search for mutations in the DDP gene, even in sporadic cases. The association of deafness-dystonia syndrome with a missense mutation provides valuable information for in vitro investigations of the functional properties of the deafness-dystonia peptide which was recently shown to be the human homolog of a yeast protein, Tim8p, belonging to a family of small Tim proteins involved in intermembrane protein transport in mitochondria.

show abstract

“…O f the other X-linked mental retardation conditions that have been as signed to a region overlapping with that o f the present dis order (see Neri 1994), there is some clinical resemblance with the Mohr-Tranebjaerg syndrome (MIM no. 304700, Tranebjaerg et al 1995) regarding ataxia, psychomotor development, deafness and visual impairment, A more de tailed mapping and, eventually, candidate gene analysis is necessary to give insight into the question of the allelism or overlap of genes involved in the described syndromes. Clinically, the present condition has most features in com mon with the infantile X-linked ataxia and deafness syn drome described by Schmidley et al (1987;M IM no.…”

Section: Resultsmentioning

confidence: 99%

Localization of the gene (or genes) for a syndrome with X-linked mental retardation, ataxia, weakness, hearing impairment, loss of vision and a fatal course in early childhood

et al. 1996

View full text Add to dashboard Cite

Linkage analysis is described in a family with X-linked m ental retardation, ataxia, weakness, floppiness, delayed m otor developm ent, absence of deep tendon re flexes, hearing im pairm ent and loss of vision (M IM no. 301835). The disease has a fatal course due to the suscep tibility of the patients to infections, especially of the res piratory tract. Clinical signs indicate impairment of the posterior columns, peripheral m otor and sensory neurons and the second and eighth cranial nerves and/or their nu clei. The involvem ent of the posterior columns of the spinal cord is further suggested by the almost complete absence of myelinated fibers therein. We localized the re sponsible gene(s) to X q21.33-q24 betw een D X S 1231 and DXS 1001 with a m axim um lod score o f 6.97. The proteolipid protein gene, which codes for two myelin proteins of the central nervous system and is located in this region, was considered as a candidate gene for this disorder. However, no m utations were found in the protein-coding part of this gene.

show abstract

A new X linked recessive deafness syndrome with blindness, dystonia, fractures, and mental deficiency is linked to Xq22.

Abstract: X linked recessive deafness accounts for only 1-7% of all childhood deafness. Only a few of the at least 28 different X linked syndromes associated with hearing

Cited by 168 publications

References 36 publications

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness–dystonia–optic atrophy syndrome

Localization of the gene (or genes) for a syndrome with X-linked mental retardation, ataxia, weakness, hearing impairment, loss of vision and a fatal course in early childhood

Contact Info

Product

Resources

About