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Table 1 Diagnostic DSD genes included in the panel

From: Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort

  Gene Locus OMIM Associated DSD Inheritance Coverage (>20×)
Gonadal development
  BMP15 Xp11.22 300247 46,XX DSD—ovarian dysgenesis AD 95%
CBX2 17q25.3 602770 46,XY DSD CGD AR 96%
DHH 12q13.12 605423 46XY PGD or CGD AR, AD 99%
DMRT1 9p24.3 602424 46,XY DSD AD: deletion 98%
DMRT2 9p24.3 604935 46,XY DSD AD: deletion 99%
FOXL2 3q22.3 608996 POI alone or with blepharophimosis, ptosis, and epicanthus inversus syndrome AD 94%
GATA4 8p23.1 600576 46,XY DSD AD 91%
NR0B1 Xp21.2 300473 46,XY GD—gain of function XL-dup 100%
    46,XX CAH with HH XLR  
NR5A1 9q33.3 184757 46,XY DSD (various) AD 100%
    46,XX POI AD  
MAP3K1 5q11.2 600982 46,XY GD AD 99%
RSPO1 1p34.3 609595 46,XX OT DSD with palmoplantar hyperkeratosis AR 94%
SOX3 Xq27.1 313430 46,XX T or OT DSD—gain of function XL: dup 92%
SOX9 17q24.3 608106 46,XY GD and campomelic dysplasia AD 95%
    46,XX T DSD—duplication AD: dup  
SRY Yp11.2 480000 46,XX T DSD—gain of function Translocation 58%*
    46,XY ovarian DSD AD  
TSPYL1 6q22.1 604714 46,XY DSD with sudden infant death syndrome AR 99%
WNT4 1p36.12 603490 46,XY ovo or OT DSD or 46,XY CGD—duplication AD: dup 99%
    46,XX T DSD AR  
    46,XX MRKH AD  
WT1 11p13 607102 Frasier syndrome and Denys-Drash AD 99%
ZFPM2 8q23.1 603693 46,XY GD AD 99%
Gonadal differentiation (androgen synthesis and action)
  AKR1C2 10p15.1 600450 46,XY DSD AR 82%
AKR1C4 10p15.1 600451 46,XY DSD AR 99%
AMH 19p13.3 600957 PMDS AR 94%
AMHR2 12q13.13 600956 PMDS AR 100%
AR Xq12 313700 46,XY DSD. Complete AIS/partial AIS, isolated hypospadia XL 97%
ARX Xp21.3 300215 X-linked lissencephaly with ambiguous genitalia XL 90%
ATRX Xq21.1 300032 46,XY DSD associated with alpha-thalassemia X-linked intellectual disability syndrome XL 99%
CDKN1C 11p15.4 600856 Genital anomalies in association with Beckwith-Wiedemann and IMAGE syndrome AD 61%
CYB5A 18q22.3 613218 46,XY DSD AR 99%
CYP11A1 15q24.1 118485 46,XY sex reversal (partial or complete) with adrenal insufficiency. CAH AR 100%
    Hypospadias AD  
CYP11B1 8q24.3 610613 46,XX DSD. CAH due to steroid 11-beta-hydroxylase deficiency AR 86%
CYP17A1 10q24.32 609300 46, XY DSD. 17,20-lyase deficiency CAH AR 100%
CYP19A1 15q21.2 107910 46, XY DSD. Aromatase deficiency AR 100%
CYP21A2 6p21.33 613815 46, XX DSD virilization—21-hydroxylase-deficient CAH AR 6%
FGFR2 10q26.13 176943 46,XY GD with craniosynotosis. Apert syndrome AD 99%
HSD17B3 9q22.32 605573 46,XY DSD—17-β-hydroxysteroid dehydrogenase III deficiency AR 100%
HSD17B4 5q23.1 233400 Perrault syndrome (with ovarian dygeneisis in 46,XX) AR 98%
HSD3B2 1p12 613890 46,XY DSD and 46,XX DSD—3-β-hydroxysteroid dehydrogenase-deficient CAH AR 99%
    Hypospadias AD  
LHCGR 2p16.3 152790 46,XY DSD—Leydig cell hypoplasia, AR 100%
    Precocious puberty (male) AD  
NR3C1 5q31.3 138040 46,XX hyperandrogenism AD 96%
POR 7q11.23 124015 Cytochrome P450 oxidoreductase deficiency AR 95%
SRD5A2 2p23.1 607306 46,XY DSD. Steroid 5-α-reductase deficiency AR 100%
    Hypospadias AD  
STAR 8p11.23 600617 46,XY DSD—cholesterol desmolase-defient CAH AR 100%
Central causes of hypogonadism
  BBS9 7p14.3 615986 Bardet-Biedl syndrome AR 96%
CHD7 8q12.2 608892 CHH or KS. CHARGE syndrome AD 99%
FGF8 10q24.32 612702 CHH or KS AD 88%
FGFR1 8p11.23 147950 CHH or KS AD 100%
FSHB 11p14.1 136530 CHH AD 98%
FSHR 2p16.3 136435 46,XX ovarian dysgenesis AR 100%
GNRH1 8p21.2 152760 CHH AR 100%
GNRHR 4q13.2 138850 CHH AR 100%
HESX1 3p14.3 601802 KS or CPHD AD 98%
KAL1 Xp22.31 300836 CHH or KS XL 97%
KISS1R 19p13.3 604161 CHH or KS AD 96%
LEP 7q32.1 164160 CHH with obesity AR 99%
LHX3 9q34.3 600577 CPHD AR 89%
PROK2 3p13 607002 CHH or KS AD 99%
PROKR2 20p12.3 607123 CHH or KS AD 100%
PROP1 5q35.3 601538 CPHD AR 98%
TAC3 12q13.3 162330 CHH AR 98%
WDR11 10q26.12 606417 CHH or KS AD 93%
Other (isolated hypospadia, cryptorchidism, MRKH):
  ATF3 1q32.3 603148 46,XY isolated hypospadias AD 97%
HOXA13 7p15.2 142959 Hand-foot uterus syndrome - MRKH in 46,XX AD 93%
    Guttmacher syndrome in 46,XY including hypospadias AD  
INSL3 19p13.11 146738 Cryptorchidism AD 99%
MAMLD1 Xq28 300120 Hypospadias XL 100%
RXFP2 13q13.1 606655 Cryptorchidism AD 96%
  1. DSD genes considered as diagnostic that were included in the targeted gene panel. These are grouped according to their main action during development (gonadal development, androgen or hormonal activity, central causes of hypogonadism or other). Gene locus is shown as well as reference number for OMIM (Online Mendelian Inheritance in Man). The associated DSD(s) are shown for each gene. CGD complete gonadal dysgenesis, PGD partial gonadal dysgenesis, POI premature ovarian insufficiency, GD gonadal dysgenesis, CAH congenital adrenal hyperplasia, HH hypogonadotrophic hypogonadism, OT ovo-testicular, T testicular, MRKH Mayer-Rokitansky-Küster-Hauser syndrome, PMDS persistent Müllerian duct syndrome, AIS androgen insensitivity syndrome, CHH congenital hypogonadotrophic hypogonadism, KS Kallmann syndrome, CPHD central pituitary hormone defect. Mode of inheritance is shown: AR autosomal recessive, AD autosomal dominant, XL X-linked, dup duplication (gain of function). The percentage coverage with greater than 20× depth is also shown