Fig. 1

TBC1D1 mutation in patients with MRKH. A Image of patient Fc-M-1 with a diagnosis of MRKH. No uterine echo was evident in the pelvic ultrasound (indicated by *) behind the bladder (denoted by B). B Image of patient Fc-M-1 with a diagnosis of MRKH. The right renal (R–R) region is enlarged. C Image of patient Fc-M-1 with a diagnosis of MRKH. The left renal (L–R) region was dysplastic and located in the left lower abdomen (pelvic ectopic kidney). The region was 4.0 cm in length. A cystic cavity measuring 1.8 * 1.6 cm was evident. The renogram showed that the left kidney had no function. D Pelvic ultrasound image of patient Fc-M-3 with a diagnosis of MRKH. B denotes bladder and U denotes aplastic uterus without rudimentary cavity. E TBC1D1 is highly expressed in the human uterus. The data were obtained from an online database (https://varsome.com/gene/TBC1D1). The red arrow denotes the expression level of TBC1D1 in the human uterus. F Sanger sequencing confirmation of the heterozygous TBC1D1 variant in patient Fc-M-1. The patient’s father (I-1) also carried the same heterozygous variant. The patient’s mother (I-2) harbored two wild-type (WT) alleles. The red arrow indicates the variant site (c.2553delC); MT, mutated allele. G The domain and mutation in TBC1D1. Full-length TBC1D1 is 1168 amino acids (aa), and includes the PID domain from aa 246 to 404 (blue box) and the catalytic Rab-GAP TBC domain from aa 800 to 994 (red box). The p.R854Efs*24 mutation results in a predicted 23-aa frameshift sequence in the protein resulting in a nonsense mutation; WT, wild type allele. (H) Sanger sequencing validating the TBC1D1 variant in patient Fc-M-3. The red arrow indicates the variant site (c.1069G>C). I The wild-type (green) and p.E357Q mutant protein (red) structure for amino acids at positions 164 to 371 were predicted by RoseTTAFold. The wild-type sequence and the p.E357Q mutant sequence were aligned by VMD software