Table 2.

HSD3B2 gene mutations causing 3β–hydroxysteroid dehydrogenase type 2 deficiency

Mutation/genotype	Sex	Clinical presentation	Comments	First author [reference]
Homozygous mutation c.73G >T(p.E25X)	Female	SW Mild virilization		Huang [61]
(L205P, p.Leu205Pro)	Male	SW Hyperpigmentation Severe hypospadias Bifid scrotum	No detectable 3βHSD activity	Moisan [16]
Compound heterogeneous mutation 186/insC/187 and (Y253N, p.Tyr253Asn)	Male	SW Severe undervirilization Hypospadia	Frames shift, missense No detectable 3βHSD activity	Simard [24, 29]
Compound heterogeneous mutation: W171X/(E142K, p.Glu142Lys)	Male	SW Severe undervirilization Hypospadia	Nonsense, missense No detectable 3βHSD activity	Simard [24, 29]
(A82P, p.Ala82Pro)	Male	SW Perineal hypospadias		Rabbani [60]
Homozygous mutation 687del27	Male	Neonatal SW Micropenis with a perineal hypospadias	Achieved normal puberty Adult spermatic characteristics were normal	Donadille [10]
687del27 homozygous mutation	Male	Perineal hypospadias Miropenis SW	No detectable 3βHSD activity	Moisan [16]
Homozygous c.687del27	Male	Severe undervirilization Low steroid production Arrested spermatogenesis Gynecomastia		Burckhardt [20]
Compound heterogeneous mutation 318 [ACA (Thr)] —>AA 273 [AAA(Lys) —>A]	Female	SW Sexual ambiguity		Zhang [30]
(T259M, p.Thr259Met)	Male	Perineal hypospadia Bifid scrotum SW	No detectable 3βHSD activity	Moisan [16]
	Female	Mild clitromegaly Premature pubarche		Marui [35]
(T259R, p.Thr259Arg)	Male	Pigmentation Hypospadias Bifid scrotum SW	No detectable 3βHSD activity	Moisan [16]
	Female	Normal genitalia with severe pigmentation SW
Compound heterozygote A82D, W230X	Female	Hypoglycemia SW		Nordenstrom [31]
(P222Q, p.Pro222Gln)	Male	Perineal hypospadias Micropenis SW	No detectable 3βHSD activity	Moisan [16]
(P155L, p.Pro155Leu)	Male	Perineal hypospadias SW	No detectable 3βHSD activity	Moisan [16]
Homozygous p.W355R (c.763 T>C)	Male	Hypospadias cryptorchidism Bifid scrotum SW	TART	Guven [63]
(A10E, p.Ala10Glu)	Male	Sexual ambiguity SW Azoospermia	Missense	Alos [15]
	Female	Normal genitalia SW/normal puberty
Homozygous p.Q334X (c.1000C>T)	Male	SW Hypospadias, small phallus, bifid scrotae, palpable gonads	TART	Alswailem [28]
	Female	SW Normal genitalia
p.R335X (c.1003C>T)	Male	SW Hypospadias Bifid scrota Palpable gonads Advanced bone maturation	Bilateral TARTs
	Female	SW Normal genitalia
W171X :Trp171 Stop	Female	SW Normal external genitilia Failure of breast development	Nonsense	Rheaume [11]
Compound heterogenous mutation W171X: Trp171 Stop and 186/insC/187	Male	SW Hypospadias	Nonsense Adequate spermatogenesis	Rheaume [11]
273ΔAA	Male	SW Ambiguous genitalia	Frameshift mutation No residual enzymatic activity	Simard [48]
Compound heterogenous mutation (L108W, p.Leu108Trp) (P186L, p.Pro186Leu)	Male	SW Hypospadias	Missense Less than 0.5% enzymatic activity	Sanchez [53]
(G15D, p.Gly15Asp)	Male	SW Hypospadias	Missense	Rheaume [49]
Compound heterozygous for T181I1 and 1105delA	Female	SW Premature pubarche, slight growth acceleration, and advanced bone age	Frameshift	Johannsen [37]
(P222T, p.Pro222Thr)	Female	SW	Missense	Pang [58]
(P341L, p.Pro341Leu)	Male	SW Micropenis		Welzel [59]
Heterozygosity.244G>A (p.Ala82Thr), 931C>T(p.Gln311*)	Female	Ambiguous genitalia		Teasdale [64]
(S213G, p.Ser213Gly)	Female	Premature pubarche at 4 y Growth acceleration	Detectable activity	Moisan [16]
(A245P, p.Ala245Pro)	Male	Sexual ambiguity	Detectable activity	Simard [24, 29]
(A10V, p.Ala10Val)	Male	Perinoscrotal hypospadia	Detectable activity (30%)	Moisan [16]
(L236S, p.Leu236Ser)	Male	Perinoscrota hypospadias Micropenis	Missense	Moisan [16]
	Female	Premature pubarche	Missense	Nayak [57]
(A245):Ala245Pro	Male	Hypospadias Bifid scrotum	Missense Detectable enzymatic activity	Simard [24]
(G129R, p.Gly129Arg)	Male	Perineal hypospadias	Missense/splice Detectable enzymatic activity	Rheaume [51]
	Female	Normal genitalia Premature pubarche
(N100S, p.Asn100Ser)	Male	Perineal hypospadias	Missense	Mebarki [55]
(Y254D, p.Tyr254Asp)	Female	Severe acne Primary amenorrhea Clitoromegaly Moderate hirsutism	Missense	Sanchez [54]
(L173R, p.Leu173Arg)	Male	Perineal hypospadias	Missense Raised as female	Russel [52]
(A82T, p.Ala82Thr)	Female	Some with no signs of CAH One patient with premature pubarche	Missense	Mendonca [50]
	Male	Perineal hypospadias
p.G250V	Female	Precocious pubarche Postnatal clitoromegaly		Baquedano [62]
(A167V, p.Ala167Val)	Female	Premature pubarche	Missense	Moisan [16]
(K216E, p.Lys216Glu)	Female	Premature pubarche	Missense	Moisan [16]
(P22H, p.Pro221His)	Female	Premature pubarche		Moisan [16]
(G294V, p.Gly294Val)	Male	Hypospadias		Moisan [16]

SW Salt wasting