Gene mutations that have dominant inheritance and cause RHD, urinary tract anomalies, and defined extrarenal symptoms have been identified in TCF2 (renal cysts and diabetes syndrome), PAX2 (renal-coloboma syndrome), EYA1 and SIX1 (branchio-oto-renal syndrome), and SALL1 (Townes-Brocks syndrome).
We traced the parental origin of SALL1 mutations in sporadic TBS by analysis of linkage between SALL1 mutations and exonic or intronic polymorphisms in 16 families with 10 different mutations.
We report on two unrelated patients with Townes-Brocks syndrome who share an identical SALL1 mutation (c.3414_3415delAT), who also have endocrine abnormalities.
We applied quantitative real time PCR to detect and map SALL1 deletions in 240 patients with the clinical diagnosis of TBS, who were negative for SALL1 mutations.Deletions were found in three families.
Sequencing of SALL1, the gene mutated in TBS, in four of the eight patients revealed one with a C --> T transition (resulting in a nonsense mutation R276X) at a previously identified mutational "hot spot."
Together, these findings suggest that the DACT1 c.1256G>A nonsense variant is causative of a specific genetic syndrome with features overlapping Townes-Brocks syndrome.
Gene mutations that have dominant inheritance and cause RHD, urinary tract anomalies, and defined extrarenal symptoms have been identified in TCF2 (renal cysts and diabetes syndrome), PAX2 (renal-coloboma syndrome), EYA1 and SIX1 (branchio-oto-renal syndrome), and SALL1 (Townes-Brocks syndrome).
Specifically, there is overlap of clinical features with other conditions, most notably Holt-Oram syndrome, a condition resulting from mutation of the TBX5 locus and Townes-Brocks syndrome, known to be caused by mutations in the SALL1 gene.