Table 4.

Phenotype and genotype of central hypogonadotropic DSD subjects with P/LP variants.

Patient ID	Age	Phenotype	Transcript ID	Genetic variants	Zygosity	Family inheritance	Inheritance mode	Pathogenicity	gnomAD frequency	Popmax
2061	15 years	Hypogonadotropic hypogonadism, hyposmia	NM_000216.2	ANOS1 del Exon 4-5	Hemi	M	XR	LP	/	/
2356	7 years	micropenis, small testes	NM_000406.2	GNRHR c.806C>T, p.Thr269Met	Homo	F + M	AR	LP	0.00001194	0.00000293 (European non-Finnish)
2955	6 years	Hypogonadotropic hypogonadism, bilateral cryptorchidism, small testes	NM_000216.2	ANOS1 c.1712G>A, p.Trp571*	Hemi	De novo	XR	P	/	/
3879	15 years	Hypogonadotropic hypogonadism, hyposmia, absence of olfactory bulb	NM_000216.2	ANOS1 c.984C>G, p.Tyr328*	Hemi	M	XR	LP	/	/
3973	11 years	Gonadal dysplasia, cryptorchidism, short stature	NM_005634.2	SOX3 c.424C>A, p.Pro142Thr	Hemi	M	XL	LP	/	/
4136	11 years	Gonadal dysplasia, hypogonadotropic hypogonadism	NM_001059.2	TACR3 c.196dupG, p.Ala66fs*84	Het	F + M	AR	LP	/	/
5175	1 year	Micropenis, short stature	NM_005270.4	GLI2 c.3463_3464delGA, p.Asp1155Arg fs*39	Het	De novo	AD	P	/	/
5589	2 years 3 months	Micropenis, cryptorchidism	NM_005270.4	GLI2 c.3137delG, p.Gly1046Ala fs*84	Het	M	AD	LP	/	/
6606	3 years	Micropenis, small testes	NM_005270.4	GLI2 c.3640C>T, p.Gln1214*	Het	M	AD	LP	/	/
12343	10 years	Micropenis, gonadal dysgenesis, short stature	NM_017780.3	CHD7 c.5211-2A>G	Het	De novo	AD	P	/	/
14317	12 years 5 months	Micropenis, hypogonadotropic hypogonadism, mild intelligence disability, absence of olfactory bulb (normal olfactory function)	NM_003106.3	SOX2 c.259A>G, p.Lys87Glu	Het	De novo	AD	LP	/	/
14376	8 years 9 months	Hypogonadotropic hypogonadis, micropenis, bilateral cryptorchidism, hyposmia	NM_000216.2	ANOS1 c.515G>A, p.Cys172Tyr	Hemi	M	XR	LP	/	/
15071	4 years 8 months	Micropenis, motor development retardation	NM_006941.3	SOX10 c.506C>T, p.Pro169Leu	Het	M	AD	LP	/	/
15128	5 months	Bilateral cryptorchidism, bilateral pinky joint malformation	NM_005996.3	TBX3 c.932dupA, p.Glu312Glyfs*6	Het	De novo	AD	P	/	/
15562	1 year 1 month	Micropenis, bilateral cryptorchidism, hyposmia	NM_006941.3	SOX10 c.506C>T, p.Pro169Leu	Het	De novo	AD	LP	/	/
16255	13 years 3 months	Bilateral cryptorchidism, micropenis, absence of olfactory bulb, intelligence disability, dysmorphic facial features (long philtrum, congenital cup ear, ocular hypertelorism), brachydactyly (finger), syndactyly (toe), abnormal brain structure	NM_023110.2	FGFR1 c.2173T>C, p.Cys725Arg	Het	De novo	AD	LP	/	/
2061	15 years	Hypogonadotropic hypogonadism, hyposmia	NM_000216.2	ANOS1 del Exon 4-5	Hemi	M	XR	LP	/	/
2356	7 years	Micropenis, small testes	NM_000406.2	GNRHR c.806C>T, p.Thr269Met	Homo	F + M	AR	LP	0.00001194	0.00000293 (European non-Finnish)
2955	6 years	Hypogonadotropic hypogonadism, bilateral cryptorchidism, small testes	NM_000216.2	ANOS1 c.1712G>A, p.Trp571*	Hemi	De novo	XR	P	/	/
3879	15 years	Hypogonadotropic hypogonadism, hyposmia, absence of olfactory bulb	NM_000216.2	ANOS1 c.984C>G, p.Tyr328*	Hemi	M	XR	LP	/	/
3973	11 years	Gonadal dysplasia, cryptorchidism, short stature	NM_005634.2	SOX3 c.424C>A, p.Pro142Thr	Hemi	M	XL	LP	/	/
4136	11 years	Gonadal dysplasia, hypogonadotropic hypogonadism	NM_001059.2	TACR3 c.196dupG, p.Ala66fs*84	Het	F + M	AR	LP	/	/
5175	1 year	Micropenis, short stature	NM_005270.4	GLI2 c.3463_3464delGA, p.Asp1155Arg fs*39	Het	De novo	AD	P	/	/
5589	2 years 3 months	Micropenis, cryptorchidism	NM_005270.4	GLI2 c.3137delG, p.Gly1046Ala fs*84	Het	M	AD	LP	/	/
6606	3 years	Micropenis, small testes	NM_005270.4	GLI2 c.3640C>T, p.Gln1214*	Het	M	AD	LP	/	/
12343	10 years	Micropenis, gonadal dysgenesis, short stature	NM_017780.3	CHD7 c.5211-2A>G	Het	De novo	AD	P	/	/
14317	12 years 5 months	Micropenis, hypogonadotropic hypogonadism, mild intelligence disability, absence of olfactory bulb (normal olfactory function)	NM_003106.3	SOX2 c.259A>G, p.Lys87Glu	Het	De novo	AD	LP	/	/
14376	8 years 9 months	Hypogonadotropic hypogonadis, micropenis, bilateral cryptorchidism, hyposmia	NM_000216.2	ANOS1 c.515G>A, p.Cys172Tyr	Hemi	M	XR	LP	/	/
15071	4 years 8 months	micropenis, motor development retardation	NM_006941.3	SOX10 c.506C>T, p.Pro169Leu	het	M	AD	LP	/	/
15128	5 months	Bilateral cryptorchidism, bilateral pinky joint malformation	NM_005996.3	TBX3 c.932dupA, p.Glu312Glyfs*6	Het	De novo	AD	P	/	/
15562	1 year 1 month	Micropenis, bilateral cryptorchidism, hyposmia	NM_006941.3	SOX10 c.506C>T, p.Pro169Leu	Het	De novo	AD	LP	/	/
16255	13 years 3 months	Bilateral cryptorchidism, micropenis, absence of olfactory bulb, intelligence disability, dysmorphic facial features (long philtrum, congenital cup ear, ocular hypertelorism), brachydactyly (finger), syndactyly (toe), abnormal brain structure	NM_023110.2	FGFR1 c.2173T>C, p.Cys725Arg	Het	De novo	AD	LP	/	/
2061	15 years	Hypogonadotropic hypogonadism, hyposmia	NM_000216.2	ANOS1 del Exon 4-5	Hemi	M	XR	LP	/	/
2356	7 years	Micropenis, small testes	NM_000406.2	GNRHR c.806C>T, p.Thr269Met	Homo	F + M	AR	LP	0.00001194	0.00000293 (European non-Finnish)
2955	6 years	Hypogonadotropic hypogonadism, bilateral cryptorchidism, small testes	NM_000216.2	ANOS1 c.1712G>A, p.Trp571*	Hemi	De novo	XR	P	/	/
3879	15 years	Hypogonadotropic hypogonadism, hyposmia, absence of olfactory bulb	NM_000216.2	ANOS1 c.984C>G, p.Tyr328*	Hemi	M	XR	LP	/	/
3973	11 years	Gonadal dysplasia, cryptorchidism, short stature	NM_005634.2	SOX3 c.424C>A, p.Pro142Thr	Hemi	M	XL	LP	/	/
4136	11 years	Gonadal dysplasia, hypogonadotropic hypogonadism	NM_001059.2	TACR3 c.196dupG, p.Ala66fs*84	Het	F + M	AR	LP	/	/
5175	1 year	Micropenis, short stature	NM_005270.4	GLI2 c.3463_3464delGA, p.Asp1155Arg fs*39	Het	De novo	AD	P	/	/
5589	2 years 3 months	Micropenis, cryptorchidism	NM_005270.4	GLI2 c.3137delG, p.Gly1046Ala fs*84	Het	M	AD	LP	/	/
6606	3 years	Micropenis, small testes	NM_005270.4	GLI2 c.3640C>T, p.Gln1214*	Het	M	AD	LP	/	/
12343	10 years	Micropenis, gonadal dysgenesis, short stature	NM_017780.3	CHD7 c.5211-2A>G	Het	De novo	AD	P	/	/
14317	12 years 5 months	Micropenis, hypogonadotropic hypogonadism, mild intelligence disability, absence of olfactory bulb (normal olfactory function)	NM_003106.3	SOX2 c.259A>G, p.Lys87Glu	Het	De novo	AD	LP	/	/
14376	8 years 9 months	Hypogonadotropic hypogonadis, micropenis, bilateral cryptorchidism, hyposmia	NM_000216.2	ANOS1 c.515G>A, p.Cys172Tyr	Hemi	M	XR	LP	/	/
15071	4 years 8 months	Micropenis, motor development retardation	NM_006941.3	SOX10 c.506C>T, p.Pro169Leu	Het	M	AD	LP	/	/
15128	5 months	Bilateral cryptorchidism, bilateral pinky joint malformation	NM_005996.3	TBX3 c.932dupA, p.Glu312Glyfs*6	Het	De novo	AD	P	/	/

AD, autosomal dominant; AR, autosomal recessive; F, father; Hemi, hemizygote; Het, heterozygote; Homo, homozygote; LP, likely pathogenic; M, mother; P, pathogenic; XL, X chromosome linked.