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ABSTRACT: To describe the first case of monozygotic twin sisters with fragile X premutation and discordance for premature ovarian failure (POF).
A descriptive case study.
Academic center.
Monozygotic twin sisters with fragile X premutation and discordance for POF.
Serum laboratory testing, fragile X premutation screening, zygosity testing, X-inactivation ratio and Southern blot studies.
Incidence of POF in this twin cohort.
Zygosity analysis using polymerase chain reaction of 15 polymorphic markers via capillary gel electrophoresis in these patients confirmed their monozygosity. X-inactivation studies were performed using the human androgen receptor (HUMARA) gene and revealed similar X-inactivation ratios for both the patient and her sister (11:89 and 12:88, respectively) from peripheral serum samples. Southern blot evaluation of the proband and her sister revealed a similar methylation pattern in which the premutation allele was unmethylated much more than the normal allele. The contribution of the premutation on the active allele as determined by Southern blot analysis was consistent between sisters.
The inactivation ratio studies and subsequent Southern blot analysis do not show differences between the patients; therefore, we are unable to identify a causative mechanism for the identical sisters' discordant phenotypes. It is possible that the inactivation ratios observed from the peripheral blood specimens obtained from the sisters do not represent the allele expression and skewing present at the level of the ovary.
Fertility and sterility 02/2011; 95(7):2431.e13-5. · 3.97 Impact Factor
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Carla M Lema Tomé,
Ryan Miller,
Clayton Bauer,
Charles Nottingham,
Chelsey Smith,
Kaitlin Blackstone,
Lauren Brown,
Rachael Bryan,
Adam Leigh, Megan Brady,
Jamie Busch,
Christopher P Turner
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ABSTRACT: Age-dependent, MK801-induced, activated caspase-3 expression in the postnatal brain is generally not observed in neurons expressing calcium-binding proteins (CaBPs), suggesting that apoptosis and calcium buffering are inversely related. In regions such as the cingulate and retrosplenial cortex, injury peaks at postnatal Day 7 (P7) and rapidly diminishes thereafter, whereas expression of calbindin (CB) and calretinin (CR) was relatively low from P0 to P7 and steadily increased from P7 to P14. At ages thereafter, CB and CR expression either remained stable then declined or rapidly declined. Parvalbumin (PV) was generally low-absent prior to P7 but expression dramatically increased from P10 onwards, peaking at P21. These studies suggest calcium entry (through N-methyl-D-aspartate receptor (NMDARs)) and buffering (by CaBPs) are integral to normal CNS maturation. Because schizophrenia is associated with glutamate hypo-function, developmental injury, and aberrant CaBP expression, our data indicate that this postnatal brain injury model may offer important insights into the nature of this disorder.
Developmental Psychobiology 10/2007; 49(6):606-18. · 2.98 Impact Factor
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Carla M. Lema Tomé,
Ryan Miller,
Clayton Bauer,
Charles Nottingham,
Chelsey Smith,
Kaitlin Blackstone,
Lauren Brown,
Rachael Bryan,
Adam Leigh, Megan Brady,
Jamie Busch,
Christopher P. Turner
[show abstract]
[hide abstract]
ABSTRACT: Age-dependent, MK801-induced, activated caspase-3 expression in the postnatal brain is generally not observed in neurons expressing calcium-binding proteins (CaBPs), suggesting that apoptosis and calcium buffering are inversely related. In regions such as the cingulate and retrosplenial cortex, injury peaks at postnatal Day 7 (P7) and rapidly diminishes thereafter, whereas expression of calbindin (CB) and calretinin (CR) was relatively low from P0 to P7 and steadily increased from P7 to P14. At ages thereafter, CB and CR expression either remained stable then declined or rapidly declined. Parvalbumin (PV) was generally low-absent prior to P7 but expression dramatically increased from P10 onwards, peaking at P21. These studies suggest calcium entry (through N-methyl-D-aspartate receptor (NMDARs)) and buffering (by CaBPs) are integral to normal CNS maturation. Because schizophrenia is associated with glutamate hypo-function, developmental injury, and aberrant CaBP expression, our data indicate that this postnatal brain injury model may offer important insights into the nature of this disorder. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 606-618, 2007.
Developmental Psychobiology 08/2007; 49(6):606 - 618. · 2.98 Impact Factor
