Table 1.
Clinical, biochemical and genetic characteristics of the studied MAMLD1 patients.
| Patient | Karyotype assigned sex |
Phenotype and origin | Gonadal function (age) | Adrenal function (age) | MAMLD1 variant | Variants after filtering by gene list (A) | Candidate variants (B) | Candidate genes (C) |
|---|---|---|---|---|---|---|---|---|
| 1 (7) |
46,XY Female |
Penoscrotal hypospadias. Small penis. Unilateral cryptorchidia. Histology: normal for age (2y). Venezuelan origin. |
Normal hCG test. | Normal Synacthen test. | p.V505A NM_005491:c.1514T>C |
547 | 9 | 7 |
| 2 (6) |
46,XY Male |
Penoscrotal hypospadias. Small penis. Testes: 2 ml. Spanish origin. |
Normal baseline T (3m). Normal hCG test (9m). |
Normal baseline (3d). |
p.A503E NM_005491:c.1508C>A | 492 | 1 | 1 |
| 3 (9) |
46,XY Female |
Penoscrotal hypospadias. Small penis. Histology: normal for age (nests of normal Leydig cells; normal fertility index (1y) Müllerian ducts. Spanish origin |
Normal baseline (12m). No hCG test. |
NA | p.S730S NM_005491:c.2190G>A | 570 | 2 | 2 |
| 4 (3) |
46,XY Female |
Female genitalia. Gonads in labia. Spanish origin. |
Normal hCG test (2y). | Normal baseline (2y). |
p.H347Q NM_005491:c.1041C>A rs62641609 |
633 | 4 | 4 |
| 5 (4) |
46,XY Male |
Penoscrotal hypospadias. Testes 2 ml. Spanish origin. |
Normal hCG test. Normal AMH (2.5y). |
Normal baseline (2.5y). |
p.H347Q NM_005491:c.1041C>A rs62641609 |
929 | 6 | 6 |
| 6 (8) |
46,XY Male |
Penoscrotal hypospadias. Small penis. Testes 1 ml. Esophageal atresia. Right aortic arch. North African origin. |
Normal prepubertal baseline T (15 m). Normal AMH. |
Normal baseline (15 m). |
p.L724V NM_005491:c.2170C>G | 710 | 16 | 16 |
| 7 (5) |
46,XY Male |
Hypospadias. Short penis. Testes 8 ml. Delayed puberty. Gynaecomastia. Fathered a boy. Swiss origin. |
Normal baseline T and gonadotropins (70y). Fathered a boy. |
Normal baseline (70y). |
p.Q501Q502 NM_005491:c.1503_1504dupCAGCAG | 429 | 5 | 5 |
| 8 | 46,XX Female |
Female external genitalia. Small ovaries and uterus, with fallopian tubes. Primary amenorrhea (15y). Histology: large amount of primordial follicles (no evidence of maturation), atresic follicles. Delayed growth. Spanish origin. |
High gonadotropins and low/normal estradiol (27y). | Normal (27y). | NM_005491:c.*126C>MIT | 574 | 14 | 13 |
All patients presented one hemizygous/heterozygous variant in MAMLD1. In parentheses: patients in Camats et al. (2015); NA, not analyzed; d, day(s); m, month(s); y, year(s). (A) Filtered by DSD-related and MAMLD1-related gene list. (B) Number of candidate variants per patient: related to sex development, DSD phenotypes, and/or in MAMLD1-related genes, and with MAF ≤ 0.01. (C) Number of candidate genes per patient: genes containing at least one candidate variant per patient.