Random X chromosome inactivation in patients with Klinefelter syndrome.

47,XXY Aneuploidy DNA methylation Sex chromosome Skewed inactivation

Journal

Molecular and cellular pediatrics
ISSN: 2194-7791
Titre abrégé: Mol Cell Pediatr
Pays: Germany
ID NLM: 101660689

Informations de publication

Date de publication:
24 Jan 2020
Historique:
received: 03 10 2019
accepted: 02 01 2020
entrez: 25 1 2020
pubmed: 25 1 2020
medline: 25 1 2020
Statut: epublish

Résumé

X chromosome inactivation (XCI) is an indispensable process in the development of human female embryos. Reportedly, XCI occurs when a blastocyst contains 10-12 embryonic progenitor cells. To date, it remains unclear whether XCI ratios are normally preserved in Klinefelter syndrome (KS) patients with 47,XXY karyotype. We examined XCI ratios in 18 KS patients through DNA methylation analysis for the polymorphic trinucleotide locus in the AR gene. The results of the KS patients were compared to previous data from healthy young women. XCI ratios in KS patients followed a normal distribution. Skewed XCI was observed in two patients, one of whom exhibited extremely skewed XCI. The frequencies of skewed and extremely skewed XCI in the KS cohort were comparable to those in healthy women. This study confirmed the rarity of skewed XCI in KS patients. These results indicate that the presence of a supernumerary X chromosome during the cleavage and early blastocyst stages does not affect the developmental tempo of embryos. Our data deserve further validation.

Sections du résumé

BACKGROUND BACKGROUND
X chromosome inactivation (XCI) is an indispensable process in the development of human female embryos. Reportedly, XCI occurs when a blastocyst contains 10-12 embryonic progenitor cells. To date, it remains unclear whether XCI ratios are normally preserved in Klinefelter syndrome (KS) patients with 47,XXY karyotype.
METHODS METHODS
We examined XCI ratios in 18 KS patients through DNA methylation analysis for the polymorphic trinucleotide locus in the AR gene. The results of the KS patients were compared to previous data from healthy young women.
RESULTS RESULTS
XCI ratios in KS patients followed a normal distribution. Skewed XCI was observed in two patients, one of whom exhibited extremely skewed XCI. The frequencies of skewed and extremely skewed XCI in the KS cohort were comparable to those in healthy women.
CONCLUSION CONCLUSIONS
This study confirmed the rarity of skewed XCI in KS patients. These results indicate that the presence of a supernumerary X chromosome during the cleavage and early blastocyst stages does not affect the developmental tempo of embryos. Our data deserve further validation.

Identifiants

pubmed: 31974854
doi: 10.1186/s40348-020-0093-x
pii: 10.1186/s40348-020-0093-x
pmc: PMC6979883
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1

Subventions

Organisme : Japan Society for the Promotion of Science
ID : 17H06248
Organisme : Japan Society for the Promotion of Science
ID : 17H03616
Organisme : Japan Agency for Medical Research and Development
ID : 18ek0109266h0002
Organisme : Japan Agency for Medical Research and Development
ID : 18ek0109278h0002
Organisme : National Center for Child Health and Development
ID : 2019-A1

Références

Am J Hum Genet. 1996 Jun;58(6):1101-8
pubmed: 8651285
J Clin Endocrinol Metab. 2004 Dec;89(12):6208-17
pubmed: 15579779
Am J Hum Genet. 1989 Dec;45(6):855-61
pubmed: 2589318
Clin Genet. 2000 Nov;58(5):353-63
pubmed: 11140834
Blood. 1996 Jul 1;88(1):59-65
pubmed: 8704202
J Androl. 2012 Sep-Oct;33(5):955-62
pubmed: 22441764
Int J Androl. 2011 Dec;34(6 Pt 2):e642-8
pubmed: 21977989
N Engl J Med. 1998 Jan 29;338(5):325-8
pubmed: 9445416
Am J Hum Genet. 1992 Dec;51(6):1229-39
pubmed: 1281384
Am J Hum Genet. 2006 Sep;79(3):493-9
pubmed: 16909387
Hum Reprod. 2001 Aug;16(8):1653-6
pubmed: 11473958
Am J Hum Genet. 1997 Dec;61(6):1353-61
pubmed: 9399909
Hum Reprod Update. 2003 Jul-Aug;9(4):309-17
pubmed: 12926525
Hum Reprod. 2019 Sep 29;34(9):1762-1769
pubmed: 31398259
Acta Paediatr Suppl. 2006 Apr;95(451):24-9
pubmed: 16720461
J Clin Endocrinol Metab. 2013 Jan;98(1):20-30
pubmed: 23118429
Mol Hum Reprod. 2010 Jun;16(6):386-95
pubmed: 20228051
J Clin Endocrinol Metab. 2005 Sep;90(9):5041-6
pubmed: 15956082
Hum Reprod. 2016 Feb;31(2):312-23
pubmed: 26621855
Blood. 2012 Mar 29;119(13):e100-9
pubmed: 22286197

Auteurs

Kenichi Kinjo (K)

Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Tomoko Yoshida (T)

Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
Department of Advanced Pediatric Medicine, Tohoku University School of Medicine, Tokyo, Japan.

Yoshitomo Kobori (Y)

Department of Urology, Saitama Medical Center, Dokkyo Medical University, Koshigaya, Japan.

Hiroshi Okada (H)

Department of Urology, Saitama Medical Center, Dokkyo Medical University, Koshigaya, Japan.

Erina Suzuki (E)

Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.

Tsutomu Ogata (T)

Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Mami Miyado (M)

Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.

Maki Fukami (M)

Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan. fukami-m@ncchd.go.jp.

Classifications MeSH