Table 1 Recurrent genetic abnormalities associated with MRKH syndrome
From: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a comprehensive update
Copy number variations (chromosomal imbalances) | ||||||
Chromosome location | Imbalance | # of CNVs reported | Size range | Suspected genes involved | Phenotypea | Ref. |
1q21 | Deletion | 3 | 0.4–4 Mb | RBM8A | Type I + II | |
Duplication | 2 | 0.26–2.7 Mb | ||||
16p11.2 | Deletion | 10 | 0.5–0.7 Mb | TBX6 | Type I + II | |
17q12 | Deletion | 13 | 1.2–1.9 Mb | LHX1, HNF1B | Type I + II | |
22q11 | Deletion | 4 | 0.39–5.24 Mb | Uncertain (TBX1 not involved in all CNVs) | Type I + II | |
Duplication | 1 | 3.5 Mb | ||||
Single nucleotide variations | ||||||
Chromosome location | Gene | Variantb | Gene function / validation | Phenotype | Ref. | |
16p11.2 | TBX6 | c.484G > A; p.Gly162Ser | The gene encodes a transcription factor involved in mesoderm formation and specification [68] | Type I + II | ||
c.622-2A > T; splice variant | ||||||
c.815G > A; p.Arg272Gln | ||||||
c.1146C > A; p.Tyr382* | ||||||
17q12 | LHX1 | c.11G > C; p.Cys4Ser | Lim1-null mice also have MA [63] | Type I | ||
c.25dup; p.Arg9Lysfs*25 | ||||||
c.790C > G; p.Arg264Gly | ||||||
c.935C > A; p.Pro312His | ||||||
c.995C > G; p.Arg332Pro | ||||||
17q21.32 | WNT9B | c.472C > G; p.Gln158Glu | Wnt9b-null mice also have MA. Wnt9b acts upstream of Wnt4 [53]. | Type I | ||
c.665G > A; p.Arg222His | ||||||
c.722G > A; p.Arg241His | ||||||
c.974G > A; p.Arg325His | ||||||
c.1029C > A; p.Cys343* | ||||||
18q11.1–2 | GREB1L | c.705G > T; p.Trp235Cys | Additional GREB1L variants of unknown significance have been reported in unrelated MRKH syndrome patients [72]. Several GREB1L variants have been reported in female fetuses with BRA and uterus/uterovaginal agenesis [72,73,74]. Greb1l-null mice also have BRA and Müllerian aplasia [73, 74]. | Type II with renal malfor-mations (familial, autosomal dominant inheritance) | ||
c.2227del; p.(Gln743Argfs*10) | ||||||