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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 [20, 58,59,60]
Duplication 2 0.26–2.7 Mb
 16p11.2 Deletion 10 0.5–0.7 Mb TBX6 Type I + II [20, 61,62,63,64]
 17q12 Deletion 13 1.2–1.9 Mb LHX1, HNF1B Type I + II [20, 58,59,60, 62, 63, 65, 66]
 22q11 Deletion 4 0.39–5.24 Mb Uncertain (TBX1 not involved in all CNVs) Type I + II [44, 58, 59, 62, 65, 67]
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 [63, 69, 70]
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 [59, 63, 71]
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 [55, 56]
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) [24, 72]
c.2227del; p.(Gln743Argfs*10)
  1. Abbrevations: BRA bilateral agenesis, CNV copy number variations, MA Müllerian aplasia, URA unilateral renal agenesis
  2. aMRKH type II also encompasses MURCS association; bTrancripts for the genes are: TBX6, NM_004608.3; LHX1, NM_005568.3; WNT9B, NM_003396.1; GREB1L, NM_001142966.2