Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic

Gene: TBX6

Green List (high evidence)

TBX6 encodes transcription-factor box 6, a transcription factor critical to paraxial mesoderm segmentation and somitogenesis during embryonic development. TBX6 haploinsufficiency is believed to drive the skeletal and kidney phenotypes associated with the 16p11.2 deletion syndrome.

Ma et al (2022) reported 16 rare variants in TBX6 from Mayer-Rokitansky-Küster-Hauser syndrome cohort (1 truncating, 15 VUS). They observed a significant mutational burden of TBX6 in affected individuals vs controls. Of the 15 variants with uncertain effects, 7 were shown to induce a loss-of-function effect through various mechanisms (i.e. impaired normal splicing of TBX6 messenger RNA, decreased protein expression, perturbed transcriptional activity, and protein mislocalization). There was observed incomplete penetrance and variable expressivity in families carrying deleterious variants.

Li et al (2022) reported 7 individuals with vertebral and rib malformations and structural kidney differences associated with heterozygous TBX6 gene deletion in trans with a hypomorphic TBX6 allele or biallelic TBX6 variants.
Sources: Literature

Created: 25 Jul 2023, 4:37 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mayer-Rokitansky-Küster-Hauser syndrome; Combined skeletal-kidney dysplasia syndrome

Publications

• PMID: 36112137, 36161696

Variants in this GENE are reported as part of current diagnostic practice