Submicroscopic copy-number variations associated with 46,XY disorders of sex development

Kon, Masafumi; Fukami, Maki

doi:10.1186/s40348-015-0018-2

Molecular and Cellular Pediatrics

Table 1 46,XY DSD-associated deletions identified by molecular cytogenetic analyses

From: Submicroscopic copy-number variations associated with 46,XY disorders of sex development

	Case/family	Patient	Size of deletion	Locus	Affected DSD-causative genes	Gonadal phenotype	External genitalia	Additional clinical features	Method	Inheritance	Reference
a) Deletions encompassing known 46,XY DSD-causative genes
	Case 1		74 kb	2p16.3	LHCGR	Testes with rete testis, epididymic structures, residual adrenal structures	Ambiguous genitalia	N.D.	aCGH	De novo	Richard et al. [8]
	Case 2		8.5 Mb	9p24.1-p24.3	DMRT1	Streak gonads with ovarian ducts	Female	MR, schizophrenia	aCGH	N.D.	Igarashi et al. [9]
	Case 3		10.6 Mb	9p23-p24.3	DMRT1	PGD with dysgerminoma	Clitoromegary	Mild MR	aCGH	N.E.	Ledig et al. [10]
	Case 4		9.7 Mb	9p23-p24.3	DMRT1	GD	N.D.	Hydrops, facial dysmorphism, limb and kidney abnormalities	aCGH	De novo	Ledig et al. [10]
	Case 5		821.6 kb	9p24.3	DMRT1	CGD	Female	None	aCGH	N.E.	Ledig et al. [10]
	Case 6		103.2 kb	9p24.3	DMRT1	CGD	Female	None	aCGH	N.E.	Ledig et al. [10]
	Case 7		9.7 Mb/duplication (26 Mb)	9p23-p24.3/9p13.1-p23	DMRT1	GD	N.D.	None	Targeted aCGH	De novo	Tannour-Louet et al. [11]
	Case 8		6.7 Mb	9p24.1-pter	DMRT1	GD	N.D.	None	Targeted aCGH	De novo	Tannour-Louet et al. [11]
	Case 9		0.26 Mb	9p24.3	DMRT1	CGD	N.D.	None	Targeted aCGH	N.D.	Tannour-Louet et al. [11]
	Case 10		0.20 Mb	9p24.3	DMRT1	GD	N.D.	None	Targeted aCGH	N.E.	Tannour-Louet et al. [11]
	Case 11		0.24 Mb	9q33.3	NR5A1 (SF1)	Abnormal germ cells, no Leydig cells	Ambiguous genitalia	N.D.	aCGH	Maternal	Harrison et al. [12]
	Case 12		3.1 to 4.8 kb	9q33.3	NR5A1 (SF1)	Leydig cell hyperplasia, scarce germ cells, carcinoma in situ	Female without uterus, clitoromegaly	N.D.	Custom MLPA	N.D.	Barbaro et al. [13]
	Case 13		0.96 Mb	9q33.3	NR5A1 (SF1)	N.D.	Clitoromegaly, shallow vaginal entrance	Ptosis	aCGH	De novo	van Silfhout et al. 2009 [14]
	Case 14		1.54 Mb	9q33.3	NR5A1 (SF1)	N.E.	Female	Mild MR, minor dysmorphisms	aCGH	De novo	Brandt et al. [15]
	Case 15		3.07 Mb	9q33.3-q34.11	NR5A1 (SF1)	Ovotestis	Clitoromegaly	Genitopatellar syndrome	aCGH	N.D.	Schlaubitz et al. [16]
	Case 16		10 Mb	11p12-p14.1	WT1	N.E.	Female	WAGR syndrome^a	aCGH	De novo	Le Caignec et al. [17]
	Case 17		18.0 Mb	2q31.1-q32.1	HOXD cluster	N.D.	Severe micropenis, hypospadias	Short stature, MR, multiple anomalies	aCGH	N.D.	Igarashi et al. [9]
	Case 18		503.2 kb	Yq11.223	AZFb-c region	CGD	Female	None	aCGH	N.D.	Ledig et al. [10]
b) Deletions in the upstream region of known 46,XY DSD-causative genes
	Case 19		1.193 Mb	17q24.2-q24.3	Upstream of SOX9	CGD	Female	Cleft palate, short stature	SNP array	N.D.	White et al. [18]
	Case 20		3.3 Mb	17q24.2-q24.3	Upstream of SOX9	CGD	Female	Acampomelic campomelic dysplasia, kyphoscoliosis	aCGH	N.D.	Ledig et al. [10]
	Family 1	Proband	240 kb	17q24.3	Upstream of SOX9	Small testis (right), streak gonad (left)	Asymmetric external genitalia, urogenital sinus with a phallus	None	MLPA/aCGH	Maternal	Benko et al. [19]
	Family 1	Cousin	240 kb	17q24.3	Upstream of SOX9	Streak gonad with gonadoblastoma (right), ovary (left)	Female	None	MLPA/aCGH	Maternal	Benko et al. [19]
	Case 21		236.3 kb	17q24.3	Upstream of SOX9	Streak gonad (right), gonadal tumor (left)	Female	None	MLPA/aCGH	Maternal	Kim et al. [20]
	Family 2	Proband	65.4 kb	17q24.3	Upstream of SOX9	Dysgenic testis^b	Ambiguous genitalia	None	MLPA/aCGH	Maternal	Kim et al. [20]
	Family 2	Sibling	65.4 kb	17q24.3	Upstream of SOX9	Dysgerminoma (right), streak gonad with a gonadoblastoma (left)	Female	None	MLPA/aCGH	Maternal	Kim et al. [20]
	Family 3	Proband	136 kb	17q24.3	Upstream of SOX9	Dysgenic gonad with a gonadoblastoma	Female	N.D.	MLPA/aCGH	Maternal	Kim et al. [20]
	Family 3	Maternal relative	136 kb	17q24.3	Upstream of SOX9	Ovarian dysgerminoma	Female	N.D.	MLPA/aCGH	Maternal	Kim et al. [20]
	Family 4	Proband	576.9 kb	17q24.3	Upstream of SOX9	CGD	Female	None	MLPA/aCGH	Maternal	Kim et al. [20]
	Family 4	Sibling	576.9 kb	17q24.3	Upstream of SOX9	CGD	Female	None	MLPA/aCGH	Maternal	Kim et al. [20]
	Case 22		35 kb	8p23.1	Upstream of GATA4	CGD	Female	Adrenal hypoplasia congenita	SNP array	N.D.	White et al. [18]
	Case 23		0.22 Mb	8p23.1	Upstream of GATA4	PGD	Ambiguous genitalia	N.D.	aCGH	Maternal	Harrison et al. [12]
	Case 24		257 kb	Xp21.2	Upstream of NR0B1 (DAX1)	Testis-like (right), streak gonad (left)	Female	None	aCGH	Maternal	Smyk et al. [21]

DSD, disorders of sex development; PGD, partial gonadal dysgenesis; CGD, complete gonadal dysgenesis; GD, gonadal dysgenesis of unknown severity; N.E., not examined; N.D., not described; MR, mental retardation; aCGH, array-based comparative genomic hybridization; MLPA, multiplex ligation-dependent probe amplification. ^aWilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome. ^bDysgenic testis with remnants of ducti deferentes and rete testis and with primitive seminiferous tubules.

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