Arid
DOI10.1136/jmedgenet-2011-100255
Disruption of a long distance regulatory region upstream of SOX9 in isolated disorders of sex development
Benko, Sabina2; Gordon, Christopher T.2; Mallet, Delphine3; Sreenivasan, Rajini4,5; Thauvin-Robinet, Christel6; Brendehaug, Atle7; Thomas, Sophie2; Bruland, Ove7; David, Michel8; Nicolino, Marc8; Labalme, Audrey3; Sanlaville, Damien3; Callier, Patrick; Malan, Valerie10; Huet, Frederic9; Molven, Anders11,12; Dijoud, Frederique13; Munnich, Arnold2,14; Faivre, Laurence6; Amiel, Jeanne2,14; Harley, Vincent4; Houge, Gunnar6,15; Morel, Yves3; Lyonnet, Stanislas1,2,13
通讯作者Lyonnet, Stanislas
来源期刊JOURNAL OF MEDICAL GENETICS
ISSN0022-2593
出版年2011
卷号48期号:12页码:825-830
英文摘要

Background The early gonad is bipotential and can differentiate into either a testis or an ovary. In XY embryos, the SRY gene triggers testicular differentiation and subsequent male development via its action on a single gene, SOX9. The supporting cell lineage of the bipotential gonad will differentiate as testicular Sertoli cells if SOX9 is expressed and conversely will differentiate as ovarian granulosa cells when SOX9 expression is switched off.


Results Through copy number variation mapping this study identified duplications upstream of the SOX9 gene in three families with an isolated 46, XX disorder of sex development (DSD) and an overlapping deletion in one family with two probands with an isolated 46, XY DSD. The region of overlap between these genomic alterations, and previously reported deletions and duplications at the SOX9 locus associated with syndromic and isolated cases of 46, XX and 46, XY DSD, reveal a minimal non-coding 78 kb sex determining region located in a gene desert 517-595 kb upstream of the SOX9 promoter.


Conclusions These data indicate that a non-coding regulatory region critical for gonadal SOX9 expression and subsequent normal sex development is located far upstream of the SOX9 promoter. Its copy number variations are the genetic basis of isolated 46, XX and 46, XY DSDs of variable severity (ranging from mild to complete sex reversal). It is proposed that this region contains a gonad specific SOX9 transcriptional enhancer(s), the gain or loss of which results in genomic imbalance sufficient to activate or inactivate SOX9 gonadal expression in a tissue specific manner, switch sex determination, and result in isolated DSD.


类型Article
语种英语
国家France ; Australia ; Norway
收录类别SCI-E
WOS记录号WOS:000297315600005
WOS关键词CAMPOMELIC DYSPLASIA ; TESTICULAR DISORDER ; NONCODING ELEMENTS ; REVERSAL ; SRY ; 46,XX ; DUPLICATION ; DELETION ; ENHANCER ; MICE
WOS类目Genetics & Heredity
WOS研究方向Genetics & Heredity
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/169340
作者单位1.Hop Necker Enfants Malad, Dept Genet, INSERM, U781, F-75743 Paris 15, France;
2.Univ Paris 05, Fac Med, Paris, France;
3.Hosp Civils Lyon, Ctr Biol & Pathol Est, Bron, France;
4.Monash Med Ctr, Prince Henrys Inst Med Res, Clayton, Vic 3168, Australia;
5.Univ Melbourne, Dept Anat & Cell Biol, Fac Med Dent & Hlth Sci, Parkvill, Australia;
6.Hop Enfants, Ctr Genet, Dijon, France;
7.Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway;
8.Hosp Civils Lyon, HFME, Bron, France;
9.CHU Dijon, Hop Enfants, Dijon, France;
10.Hop Necker Enfants Malad, AP HP, Serv Histoembryocytogenet, F-75743 Paris 15, France;
11.Univ Bergen, Gade Inst, Bergen, Norway;
12.Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway;
13.Hosp Civils Lyon, Ctr Biol Est, Serv Anatomopathol, Bron, France;
14.Hop Necker Enfants Malad, AP HP, Dept Genet, F-75743 Paris 15, France;
15.Univ Bergen, Dept Clin Med, Bergen, Norway
推荐引用方式
GB/T 7714
Benko, Sabina,Gordon, Christopher T.,Mallet, Delphine,et al. Disruption of a long distance regulatory region upstream of SOX9 in isolated disorders of sex development[J],2011,48(12):825-830.
APA Benko, Sabina.,Gordon, Christopher T..,Mallet, Delphine.,Sreenivasan, Rajini.,Thauvin-Robinet, Christel.,...&Lyonnet, Stanislas.(2011).Disruption of a long distance regulatory region upstream of SOX9 in isolated disorders of sex development.JOURNAL OF MEDICAL GENETICS,48(12),825-830.
MLA Benko, Sabina,et al."Disruption of a long distance regulatory region upstream of SOX9 in isolated disorders of sex development".JOURNAL OF MEDICAL GENETICS 48.12(2011):825-830.
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