Co-occurrence of mutations in both dystrophin- and androgen-receptor genes is a novel cause of female Duchenne muscular dystrophy

Katayama, Yoshinori; Tran, Van Khanh; Hoan, Nguyen Thi; Zhang, Zhujun; Goji, Katsumi; Yagi, Minoru; Takeshima, Yasuhiro; Saiki, Kayoko; Nhan, Nguyen Thu; Matsuo, Masafumi

doi:10.1007/s00439-006-0159-4

Cited by 34 publications

(23 citation statements)

References 6 publications

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“…To our knowledge, several different genetic abnormalities have been documented for female DMD and the milder allelic form Becker muscular Dystrophy (BMD): (1) an X-autosome reciprocal translocation and a preferential inactivation of the normal X-chromosome (Verellen-Dumoulin et al 1984); (2) in a classical 45, X0 karyotype of Turner syndrome, simultaneously, the only X-chromosome with a dystrophin mutation (Chelly et al 1986); (3) skewed X inactivation in the normal X-chromosome of the female DMD mutation carriers. (Azofeifa et al 1995); (4) uniparental disomy of female with DMD mutation in both X-chromosome (Quan et al 1997); (5) co-occurrence of mutations in both dystrophin and androgen-receptor genes in the patient (Katayama et al 2006); and (6) girl with homozygous dystrophin mutation caused by consanguinity, whose parents have the same mutations in the DMD gene (Fujii et al 2009). While our patient is similar to the case of Turner syndrome with the dystrophin gene mutation in the remaining X chromosome as originally reported (Chelly et al 1986), the karyotype of our patient is unique.…”

Section: Discussionmentioning

confidence: 99%

Duchenne Muscular Dystrophy in a Female Patient with a Karyotype of 46,X,i(X)(q10)

et al. 2010

Tohoku J. Exp. Med.

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Duchenne muscular dystrophy (DMD) is a severe recessive X-linked form of muscular dystrophy caused by mutations in the dystrophin gene and it affects males predominantly. Here we report a 4-year-old girl with DMD from a healthy family, in which her parents and sister have no DMD genotype. A PCR-based method of multiple ligation-dependent probe amplification (MLPA) analysis showed the deletion of exons 46 and 47 in the dystrophin gene, which led to loss of dystrophin function. No obvious phenotype of Turner syndrome was observed in this patient and cytogenetic analysis revealed that her karyotype is 46,X,i(X)(q10). In conclusion, we describe the first female patient with DMD who carries a de novo mutation of the dystrophin gene in one chromosome and isochromosome Xq, i(Xq), in another chromosome.

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Section: Discussionmentioning

confidence: 99%

Duchenne Muscular Dystrophy in a Female Patient with a Karyotype of 46,X,i(X)(q10)

et al. 2010

Tohoku J. Exp. Med.

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“…If AHC is diagnosed in a female, it is important to establish whether there is a normal female karyotype, as females with 46XY karyotypes or Turner syndrome can manifest X-linked conditions 14 – 17. In the presence of a 46XX karyotype, autosomal recessive causes of AHC (such as StAR, SF1, ( NR5A1 ) mutations) should be considered 18 19…”

Section: Discussionmentioning

confidence: 99%

“…Glycerol kinase (GK) activity was measured in the cells after 2–3 min pre-treatment by digitonin using the GK catalysed conversion of [U-14C]glycerol to [U-14C]glycerol-3-phosphate as described before 9…”

Section: Methodsmentioning

confidence: 99%

Skewed X inactivation is associated with phenotype in a female with adrenal hypoplasia congenita

Shaikh

Boyes

Kingston

et al. 2008

Journal of Medical Genetics

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Adrenal hypoplasia congenita (AHC) can occur due to deletions or mutations in the DAX 1 (NR0B1) gene on the X chromosome (OMIM 300200). This form of AHC is therefore predominantly seen in boys. Deletion of the DAX 1 gene can also be part of a larger contiguous deletion including the centromeric dystrophin and glycerol kinase (GK) genes. We report a girl with a de novo deletion at Xp21.2 on the maternal chromosome, including DAX1, the GK gene and 3′ end of the dystrophin gene, who presented with salt losing adrenal insufficiency and moderate developmental delay, but relatively mild features of muscular dystrophy. Investigation using the androgen receptor as a marker gene identified skewed inactivation of the X chromosome. In the patient’s leucocytes, the paternal X chromosome was completely inactive, but in muscle 20% of the active chromosomes were of paternal origin. Thus skewed X inactivation (deletion on the active maternal X chromosome with an inactive paternal X chromosome) is associated with AHC in a female. Variability in X inactivation between tissues may account for the pronounced salt loss and adrenal insufficiency but mild muscular dystrophy.

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“…Clinical presentation ranges in severity from a mild, BMD-like appearance to DMD-like disease, and may include symptoms such as muscle weakness and cardiomyopathy [26-29]. One simple explanation for these occurrences is the presence of only one X chromosome in manifesting carriers, as seen in Turners Syndrome patients [30-32] and in at least one XY male pseudohermaphrodite with female secondary sex characteristics [33]. Uniparental disomy of the X chromosome harboring the defective DMD locus has also been found in symptomatic female carriers [34].…”

Section: Overview Of Genetic Variation In Dmdmentioning

confidence: 99%

Comparative Genomics of X-linked Muscular Dystrophies: The Golden Retriever Model

Brinkmeyer-Langford

Kornegay

2013

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Duchenne muscular dystrophy (DMD) is a devastating disease that dramatically decreases the lifespan and abilities of affected young people. The primary molecular cause of the disease is the absence of functional dystrophin protein, which is critical to proper muscle function. Those with DMD vary in disease presentation and dystrophin mutation; the same causal mutation may be associated with drastically different levels of disease severity. Also contributing to this variation are the influences of additional modifying genes and/or changes in functional elements governing such modifiers. This genetic heterogeneity complicates the efficacy of treatment methods and to date medical interventions are limited to treating symptoms. Animal models of DMD have been instrumental in teasing out the intricacies of DMD disease and hold great promise for advancing knowledge of its variable presentation and treatment. This review addresses the utility of comparative genomics in elucidating the complex background behind phenotypic variation in a canine model of DMD, Golden Retriever muscular dystrophy (GRMD). This knowledge can be exploited in the development of improved, more personalized treatments for DMD patients, such as therapies that can be tailor-matched to the disease course and genomic background of individual patients.

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Co-occurrence of mutations in both dystrophin- and androgen-receptor genes is a novel cause of female Duchenne muscular dystrophy

Cited by 34 publications

References 6 publications

Duchenne Muscular Dystrophy in a Female Patient with a Karyotype of 46,X,i(X)(q10)

Duchenne Muscular Dystrophy in a Female Patient with a Karyotype of 46,X,i(X)(q10)

Skewed X inactivation is associated with phenotype in a female with adrenal hypoplasia congenita

Comparative Genomics of X-linked Muscular Dystrophies: The Golden Retriever Model

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