Table 2.
Genes reported with recurrent a sequence variation associated with MRKH syndrome.
| Gene | Chromosomal location | Zygosity | Variants reported | Variant type | MRKH type | Other phenotypes/entities associated with gene | Ref. |
|---|---|---|---|---|---|---|---|
| GREB1L | 18q11.1-q11.2 | Monoallelic | 30 | Missense (19) Frameshift (5) Splice-site (3) Stop-gain (2) Deletion (1) |
Type II (22) Type 1 (8) | CAKUT (renal agenesis/renal hypodysplasia [OMIM #617805]), hearing loss (OMIM #619274), heart malformation, other UVMs | (98, 99, 101, 102, 109, 110) |
| TBX6 | 16p11.2 | Monoallelic/biallelic b (111) | 21 | Missense (16)
c
Splice-site (4) Stop-gain (1) |
Type II (13) Type I (12) | Scoliosis, spondylocostal dysostosis (OMIM #122600), CAKUT | (72, 75, 103, 105, 111, 112) |
| PAX8 | 2q14.1 | Monoallelic | 11 | Missense (6) Frameshift (2) Stop-gain (2) Splice-site (1) |
Type I (11) | Thyroid hypoplasia/dysgenesis (OMIM #218700) | (75, 98) |
| SHOX | Xp22.33 | Monoallelic | 10 | Duplication (8) Missense (2) | Type I (6) Type II (4) |
Leri-Weill dyschondrosteosis (OMIM #127300) | (62, 64, 103) |
| WNT9B | 17q21.32 | Monoallelic/biallelic b (113) | 9 | Missense (7) Stop-gain (1) Regulatory (1) |
Type I (8) | CAKUT, cleft lip/palate, other UVMs | (98, 103, 113, 114) |
| WNT4 | 1p36.12 | Monoallelic | 7 | Missense (7) | Type I (6) Type II (1) |
Müllerian aplasia and hyperandrogenism (OMIM #158330), other UVMs | (103, 115–118) |
| LHX1 | 17q12 | Monoallelic | 6 | Missense (5) Frameshift (1) | Type I (2) Type II (1) NS (3) |
– | (72, 85, 119, 120) |
| LRP10 | 14q11.2 | Monoallelic/biallelic b | 5 | Missense (5) | Type I (3) Type II (1) |
– | (74, 103) |
| HNF1B | 17q12 | Monoallelic | 4 | In-frame deletion (2) Frameshift (1) Deletion (1) |
Type II | Renal cysts and diabetes syndrome/MODY5 (OMIM #137920) | (51, 52, 121) |
| LAMC1 | 1q25.3 | Monoallelic | 4 | Missense (4) | Type I (3) Type II (1) |
– | (103) |
| BMP4 | 14q22.2 | Monoallelic | 3 | Stop-gain (2) Splice-site (1) |
Type I (2) Type II (1) |
Microphthalmia (OMIM #607932, cleft lift/palate (OMIM #600625) | (75) |
| CTNNA3 | 10q21.3 | Monoallelic | 3 | Deletion (3) | Type II (2) Type I (1) | Arrhythmogenic right ventricular dysplasia (OMIM #615616) | (73) |
| ESR1 | 6q25.1-q25.2 | Monoallelic | 3 | Missense (2) Regulatory (1) | Type I | Estrogen resistance (OMIM #615363), breast cancer | (122) |
| MMP14 | 14q11.2 | Monoallelic | 3 | Missense (2) Duplication (1) | Type I (2) Type II (1) |
– | (35, 103) |
| RARA | 17q21.2 | Monoallelic/biallelic b | 3 | Missense (3) | Type I | Acute promyelocytic leukemia | (103) |
| BMP7 | 20q13.31 | Monoallelic | 2 | Frameshift (1) Splice-site (1) |
Type I | – | (75) |
| DLG5 | 10q22.3 | Monoallelic | 2 | Missense (1) Stop-gain (1) |
Type I+II | CAKUT | (104, 123) |
| HOXA10 | 7p15.2 | Monoallelic | 2 | Missense (1) Frameshift (1) | Type I+II | Other UVM | (75, 103) |
| KMT2D | 12q13.12 | Monoallelic | 2 | Missense (2) | Type I+II | Kabuki syndrome (OMIM# 147920) | (104) |
| MKKS | 20p12.2 | Monoallelic | 2 | Missense (2) | Type 2 | Bardet-Biedl syndrome (OMIM #605231), McKusick-Kaufman syndrome (OMIM #236700) | (74) |
| MYCBP2 | 13q22.3 | Monoallelic | 2 | Missense (2) | Type I | – | (97) |
| PKD1 | 16p13.3 | Monoallelic | 2 | Missense (1) Stop-gain (1) |
Type I+II | Polycystic kidney disease (OMIM #173900) | (123) |
| SPECC1L | 22q11.23 | Monoallelic | 2 | Missense (2) | Type 2 | Teebi hypertelorism syndrome (OMIM #145420) | (74) |
| TBC1D1 | 4p14 | Monoallelic | 2 | Missense (1) Frameshift (1) | Type I+II | CAKUT | (104) |
a
Two or more reported sequence variations in the gene. Non-recurrent candidate variants are listed in Supplementary Table S1 .
b
Two variants reported in one case. Phasing was not done to determine trans or cis configuration.
c
Including two polymorphisms (rs56098093 and rs201231713).
CAKUT, congenital anomalies of the kidneys and urinary tracts; MODY5, maturity-onset diabetes of the young type 5; NS, not stated; OMIM, Online Mendelian Inheritance in Man; UVM, uterovaginal malformations.