A novel MED14 variant is associated with VACTERL association in a human patient and in a mouse model (IMAGE)
Caption
(A) Mesocardia shown by chest CT. (B) Polydactyly of the right hand located on the lateral side of the right thumb, detected by physical examination and X-ray imaging. (C) Congenital absence of the sacrococcyx (on the right, with a normal sacrococcyx on the left for comparison) in the sagittal CT image. (D) Imperforate anus (left) and hypospadias (right) identified in physical examination. (E) Rectourethral fistula, demonstrated by colon contrast examination and simultaneous cystourethrography (left), as well as vesicoureteral reflux shown by cystourethrography (middle), and the orifice of the rectourethral fistula indicated by colonoscopy during the anoplasty (right). (F, G) Sanger sequencing validation of the point mutation in the patient, his mother, and his maternal grandfather (F), along with the family pedigree of the patient showing the segregation of the MED14 mutant allele (G), are illustrated. (H) Examination of visceral organs in 3-month-old mice revealed mesocardia in I556V mutants. (I, J) Digit lengths in WT and I556V MED14 mice were measured 3 months after birth. A representative image of shorten digits in I556V mutants (I) and a summary of measurements (J) are shown, where D1 denotes the digit closest to the bottom of the image, and the p values were determined by the unpaired two-tailed Student’s t-test. (K) Micro-CT experiments showed incomplete formation of the coccygeal vertebrae in about 20% of I556V mutant mice at E18.5. The affected area was zoomed in to provide a better view, with arrows pointing at the missing part of the coccygeal vertebrae (highlighted with a dotted line). (L) HE staining (left) and PAS staining (right) at E18.5 indicated a reduction in glomerulus size in some I556V mutant mice. Glomeruli are highlighted with arrows. Scale bar, 100 μm. (M) Measurement of glomerulus size in WT and med14 mutants at E18.5. ∗P < 0.05, with p values determined by the unpaired two-tailed Student’s t-test.
Credit
Jingwen Liu, Xuelai Liu, Feifei Li, Yujie Wang, Liping Yang, Meijia Zhang, Xinyu He, Ting Zhang, Ying Yi Zhang, Qiang Wang
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