Table 1 Phenotypes, genotypes, and investigation of gonadal function in 13 children with pathogenic variants in the DHX37 gene
Variable | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | Patient 12 | Patient 13 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Sex of rearing | Female | Female | Female | Female | Female | Female | Female | Female | Female | Male | Male | Male | Male |
Karyotype | XY | XY | XY | XY | XY | XY | XY | XY | XY | XY | XY | XY | XY |
Age at presentation | 20 years | 3 years | 16 years | 15 years | 15.5 years | Birth | NA | Birth | Birth | Birth | Birth | Birth | Birth |
Diagnosis | Gonadal dysgenesis | Gonadal dysgenesis | Gonadal dysgenesis | Gonadal dysgenesis | Gonadal dysgenesis | Gonadal dysgenesis | 46,XY DSD | 46,XY DSD | Gonadal dysgenesis | TRS | TRS | TRS | TRS |
Phenotype, external genitalia | Female, primary amenorrhea | Female | Female, primary amenorrhea | Female, discrete fusion of labia minora | Female, absence of puberty, discrete fusion of labia minora | Female, partial fusion of labia minora | Female, poorly developed labia | Virilized female, ambiguous genitalia | Ambiguous genitalia | Male, micropenis and bilateral cryptorchidism | Male, micropenis, hypospadias; unilateral cryptorchidism (L); small palpable testis (R) | Male, severe micropenis; cryptorchidism | Male, bilateral cryptorchidism |
Internal genitalia | No Müllerian structures, Wolffian structures present | Urogenital sinus | No Müllerian structures, Wolffian structures present | Fallopian tube-like structures and epididymis on each side | Vagina present, absent uterus, Wolffian structures present (both sides) | Vagina 16–17 mm long and 6–7 mm wide not opened, absent uterus; no gonads present | Absent uterus and vagina | Vagina present, absent uterus, Wolffian structures present | Vaginal septum and uterus didelphys | No Müllerian structures | Vagina present | Absent vagina and uterus; bilateral epididymal-like structures | Absent gonads with vas deferens present (12 years) |
Gonadal position | - | Abdominal cavity | - | - | - | - | - | - | - | L: Inguinal canal, R: abdominal cavity | - | - | - |
Gonadal histology | Homogeneous fibrous tissues associated with a rete testis on both sides | Bilateral fibrous gonads, duct-like structures, fragments of uterine tube | R: Small nodule of fibrous tissue; L: fibrous tissue with rare tubule-like structures | No gonadal tissue present | Homogeneous fibrous tissue | L: No gonad tissue, remnants of ductus deferens; R: no gonad tissue, remnants of epididymis tissue | NA | NA | NA | No gonadal tissue; remnants of epididymis, ductus deferens | NA | L: Homogeneous fibrous tissue; R: no gonadal tissue | NA |
LH (U/liter) | - | ||||||||||||
Value | 23.1 | 7.2 (4 years) | 18 | 17 | 20 | 0.7 (1 week) 3.3 (5 months) | NA | NA | NA | 0.6 (1 week) | 0.5 (28 days) | <0.4 (10 days) | NA |
Reference range | 2.4–13 | Tanner 1: 0.03–0.55 | 2.4–13 | 2.4–13 | 2.4–13 | 0.2–0.5 | 0.2–0.5 | 0.2–0.5 | 0.2–0.5 | ||||
FSH (U/liter) | |||||||||||||
Value | 61.5 | 90.9 (4 years) | 56 | 45 | 50 | 1.2 (1 week) 54.4 (5 months) | NA | NA | NA | 10.7 (1 week) | 8.9 (28 days) | 26.7 (5 years) | 100 (2 years) |
Reference range | ND–13.5 | 0.7–3.39 | ND–13.5 | ND–13.5 | ND–13.5 | ND–2.0 | ND–2.0 | ND–2 | ND–2 | 0.22–1.92 | |||
T (ng/ml) | |||||||||||||
Value | 0.29 | <0.025 (4 years) | <0.25 | <0.25 | <0.25 | 0.25 (1 weeks) <0.19 (5 months) | NA | NA | NA | 0.16 (1 weeks) 2 (9 weeks) | 0.1 (Basal and after HCG 1500 ui x3) | 0.2 (10 days) | 0.7 (11 years) |
Reference range | 2.70–9.00 | 0.02–0.23 | 2.70–9.00 | 2.70–9.00 | 2.70–9.00 | 0.1–0.5 0.02–0.2 | 0.1–0.5 0–8–3.3 | 0.2–0.5 | 0.7–1.7 | (0.4–19) | |||
AMH (ng/ml) | |||||||||||||
Value | 0.29 | 0.06 (4 years) | NA | 0.65 | NA | 0.01 (5 months) | NA | NA | NA | NA | NA | 0.0 | <0.01 (11 years) |
Reference range | 32.77–262.69 | 105–270 | 7.4–243 | ||||||||||
Ancestry | European | European | European | European | European | European | European | European | European | European | European | European | European |
DHX37 pathogenic variant and inheritance | c.G2021A p.R674Q unknown | c.G2021A p.R674Q de novo | c.G923A p.R308Q de novo | c.C911T p.T304M maternal | c.C911T p.T304M de novo, absent in unaffected XY sib | c.G1001T p.R334L de novo | c.G923A p.R308Q unknown | c.G923A p.R308Q unknown | c.G923A p.R308Q unknown | c.C1877T p.S626L unknown | c.C1000T p.R334W unknown | c.G923A p.R308Q de novo | c.G3089A p.G1030E unknown |
