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

Shaikh MG, Boyes L, Kingston H, Collins R, Besley GT, Padmakumar B, Ismayl O, Hughes I, Hall CM, Hellerud C, Achermann JC, Clayton PE - J. Med. Genet. (2008)

Bottom Line: Deletion of the DAX 1 gene can also be part of a larger contiguous deletion including the centromeric dystrophin and glycerol kinase (GK) genes.Investigation using the androgen receptor as a marker gene identified skewed inactivation of the X chromosome.Thus skewed X inactivation (deletion on the active maternal X chromosome with an inactive paternal X chromosome) is associated with AHC in a female.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Royal Manchester Children's Hospital, Manchester, M27 4HA, UK.

ABSTRACT
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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Linkage analysis in the parents and proband using marker DI671 situated in intron 67 of the dystrophin gene and therefore within the area deleted in the proband. Only one allele is detected in the proband and this is equivalent in size to her father’s marker at this locus, confirming the deletion is carried on her maternally inherited X chromosome.
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JMG-45-09-e1-f04: Linkage analysis in the parents and proband using marker DI671 situated in intron 67 of the dystrophin gene and therefore within the area deleted in the proband. Only one allele is detected in the proband and this is equivalent in size to her father’s marker at this locus, confirming the deletion is carried on her maternally inherited X chromosome.

Mentions: Linkage analysis, using marker DI671 situated in intron 67 of the dystrophin gene and therefore within the region deleted in the patient, was performed. Only one allele was detected in the patient, corresponding to the paternal allele, confirming that the de novo deletion was carried on her maternally inherited X chromosome (fig 4).


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

Shaikh MG, Boyes L, Kingston H, Collins R, Besley GT, Padmakumar B, Ismayl O, Hughes I, Hall CM, Hellerud C, Achermann JC, Clayton PE - J. Med. Genet. (2008)

Linkage analysis in the parents and proband using marker DI671 situated in intron 67 of the dystrophin gene and therefore within the area deleted in the proband. Only one allele is detected in the proband and this is equivalent in size to her father’s marker at this locus, confirming the deletion is carried on her maternally inherited X chromosome.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2602739&req=5

JMG-45-09-e1-f04: Linkage analysis in the parents and proband using marker DI671 situated in intron 67 of the dystrophin gene and therefore within the area deleted in the proband. Only one allele is detected in the proband and this is equivalent in size to her father’s marker at this locus, confirming the deletion is carried on her maternally inherited X chromosome.
Mentions: Linkage analysis, using marker DI671 situated in intron 67 of the dystrophin gene and therefore within the region deleted in the patient, was performed. Only one allele was detected in the patient, corresponding to the paternal allele, confirming that the de novo deletion was carried on her maternally inherited X chromosome (fig 4).

Bottom Line: Deletion of the DAX 1 gene can also be part of a larger contiguous deletion including the centromeric dystrophin and glycerol kinase (GK) genes.Investigation using the androgen receptor as a marker gene identified skewed inactivation of the X chromosome.Thus skewed X inactivation (deletion on the active maternal X chromosome with an inactive paternal X chromosome) is associated with AHC in a female.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Royal Manchester Children's Hospital, Manchester, M27 4HA, UK.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus