(a) (a)

Family		Family A					Family B		Family C				Family D					Family E
Mutation types		Duplication					Duplication		Deletion				Deletion					Deletion
The promoter involved in CYP19A1 overexpression		CYP19A1					CYP19A1		CYP19A1				DMXL2					DMXL2
Case		Case 1	Case 2		Case 3		Case 4		Case 5		Case 6		Case 7	Case 8		Case 9		Case 10
Age at examination (year)		66	15		20		15		15		13		42	9		12		13
<Phenotypic findings>
Gynecomastia (tanner breast stage)		2	2		2		3		4		4		4	3		4		4
Onset of gynecomastia (year)		13	13		10		11		12		11		11	7		9		10
Mastectomy (year)		No	Yes (15)		No		Yes (15)		Yes (15)		Yes (13)		No	No		Yes (12)		Yes (13)
Testis (ml)		N.E.	12		12		12		12		12		N.E.	3		12		20
Pubic hair (tanner stage)		N.E.	2-3		4		5		4		3		N.E.	1		3		4
Facial hair		Normal	Scarce		Scarce		Normal		Absent		Absent		N.E.	Absent		Absent		Absent
Height (SDS)a		−1.2	−0.3		+0.4		+0.8		−2.0		−1.0		−1.6	+2.7		±0		+1.8
Bone age (year)b		N.E.	N.E.		N.E.		16.0		16.0		13.5		N.E.	13.0		15.0		17.0
Fertility (spermatogenesis)		Yes	?		(Yes)h		?		?		?		Yes	?		?		?
<Endocrine findings>c		B	B	S	B	S	B	S	B	S	B	S	B	B	S	B	S	B	S
<At Dx>	Stimulus
LH (mIU/mL)	GnRHe	3.8	2.3	14.3	2.1	17.0	2.4	29.4	1.9	40.6	1.8	69.2		1.1	11.5	0.6	39.5	6.7	14.8
LH (mIU/mL)	GnRH (after priming)f		1.8	9.5	1.3	10.7
FSH (mIU/mL)	GnRHe	1.7	3.1	5.3	<0.5	1.2	0.9	2.4	1.4	4.2	2.0	7.8		3.2	6.6	0.6	2.9	0.7	1.0
FSH (mIU/mL)	GnRH (after priming)f		2.6	3.2	<0.5	0.9
Prolactin (ng/ml)			4.3		5.3				8.2		9.1			11.3		18.8
Δ4A (ng/mL)		0.5			1.1		1.2						0.6			0.7		2.4	2.9
T (ng/mL)	hCGg	2.9	1.6		2.2		4.0		2.6	7.2	1.4	7.9		0.6	3.6	2.4		3.2	9.7
DHT (ng/mL)		0.4			0.2													0.4	1.2
Inhibin B (pg/mL)		61.6			74.6		83.5		75.2
E1 (pg/mL)		157			120		124						57			63		53
E2 (pg/mL)		29	15		22		59		56		38		24	19		25		58
E2/T ratio (×103)		10.0	9.4		10.0		14.8		21.5		27.1			31.7		10.4		18.1