Molecular Studies on Small Ring X Chromosome in a Female with a Severe Phenotype

Approximately 8% of Turner syndrome patients are mosaic for a small ring X chromosome. Small ring X-chromosomes can be associated with a severe phenotype uncharacteristic of Turner syndrome if the ring X stays active due to loss of X chromosome inactivation-specific transcript (XIST) gene, or there is no expression of the XIST gene locus. We report on our molecular findings of small ring X chromosome in a baby girl who manifested a severe phenotype. The propositus was a one-month-old Taiwanese baby girl who manifested cyanosis, apnea, recurrent pneumonia and dysmorphic facial features at the time of admission to the hospital. To determine if the XIST gene on the ring X chromosome is fully expressed, RTPCR analysis was performed and the amplified products were subjected to automated sequencing and tested for mutations in the XIST and androgen receptor (AR) transcripts. The inactivation status of the ring X was also established by analysis of DNA methylation at the AR gene. Blood chromosome studies revealed the presence of mosaic 46, X, +r(X)[39]/45, X[11]. FISH studies further confirmed that the small ring is derived from an X chromosome and contains the XIST gene locus, Our data supported that XIST and AR genes are expressed, but the AR assay as an indicator of X inactivation status did not support full inactivation of the r(X). Amplification of the AR gene was poor when the patient’s DNA was tested by digestion with HpaII and undetectable by digestion with MspI,. This indicates that the r(X) in the patient may be partially active despite the fact that the XIST gene on the r(X) appears to be expressed. Our data suggested that transcription of an XIST gene alone, although required, may not be sufficient to initiate X inactivation in this case. There may be other factors, which interact with the XIST gene and involve in the X inactivation process. Alternatively, there is a mixed population of r(X) cells, in which the XIST gene locus is expressed in some, but not in all of them.

並列關鍵字

Turner syndrome ； X inactivation ； ring X-chromosome ； DNA methylation ； XIST gene ； AR gene ； GAPDH gene

國際替代計量

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