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| Status |
Public on Oct 08, 2019 |
| Title |
Heterozygous deletion of the SHOX gene enhancer in two females with clinical heterogeneity associating with skewed XCI and escaping XCI |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
Skewed X-chromosome inactivation (XCI) plays an important role in the phenotypic heterogeneity of X-linked disorders. However, the role of skewed XCI in XCI–escaping gene SHOX regulation is unclear. Here, we focused on a heterozygous deletion of SHOX gene enhancer with clinical heterogeneity. Using SNP array, we detected that the female proband with Leri-Weill dyschondrosteosis (LWD) carried an 857 kb deletion on Xp22.3 (encompassing SHOX enhancer) and a 5,707 kb large-fragment deletion on Xq25q26. XCI analysis revealed that the X-chromosome with the Xq25q26 large-fragment deletion was completely inactivated, which forced the complete activation of the other X-chromosome carrying SHOX enhancer deletion. While the Xp22.3 deletion locates on the escaping XCI region, under the combined action of skewed XCI and escaping XCI, transcription of SHOX gene was mainly from the activated X-chromosome with SHOX enhancer defect, involving in the formation of LWD phenotype. Interestingly, this SHOX enhancer deletion was inherited from her healthy mother, who also demonstrated completely skewed XCI. However, the X-chromosome with SHOX enhancer deletion was inactivated, and the normal X-chromosome was activated. Combing with escaping XCI, her phenotype was almost normal. In summary, this study was a rare report of SHOX gene enhancer deletion in a family with clinical heterogeneity due to skewed inactivation of different X-chromosomes, which can help in the genetic counseling and prenatal diagnosis of disorders in females with SHOX defect.
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| Overall design |
Karyotyping and SNP array were performed and showed the presence of an 857kb deletion in Xp22.33 (chrX:784,064-1,640,746) in the male fetus III1. To verify the results, SNP array was also performed on samples of the pregnant woman II2 and her husband II1. Surprisingly, not only a deletion of 857 kb in Xp22.33, but also a 5,707 kb deletion (chrX:127,915,006-133,621,667) in Xq25q26.3 was observed in the woman
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| Contributor(s) |
Sun Y, Dong M |
| Citation(s) |
31781162 |
| Submission date |
Oct 07, 2019 |
| Last update date |
Dec 04, 2019 |
| Contact name |
yixi sun |
| E-mail(s) |
sunyixi123456@163.com
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| Phone |
+86-571-89 991 860
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| Organization name |
Zhejiang University
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| Street address |
XUESHI ROAD 1
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| City |
hangzhou |
| State/province |
zhejiang |
| ZIP/Postal code |
310006 |
| Country |
China |
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| Platforms (1) |
| GPL16131 |
[CytoScanHD_Array] Affymetrix CytoScan HD Array |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA576166 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE138489_RAW.tar |
374.4 Mb |
(http)(custom) |
TAR (of CEL, CYCHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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