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

Gene: DACT1

I don't know

PMID 36066768 identified 7 different heterozygous missense variants in 8 individuals with renal abnormalities. 6 also had extrarenal anomalies which the authors claimed overlapped Townes-Brookes syndrome. Parents were tested in 7/8 families and all variants were inherited. One family was consanguineous and both parents were carriers. All variant-positive parents were either unaffected or unknown affected status, except for one who had skeletal abnormalities. Gnomad het counts range from novel (3 variants) to 89 hets. 2 variants are LB in ClinVar, athough the authors have classified them as LP and VUS.

Created: 6 Oct 2022, 4:04 a.m. | Last Modified: 6 Oct 2022, 4:04 a.m.

Panel Version: 0.114

Phenotypes
Townes-Brocks syndrome 2 MONDO:0054582

Publications

• 36066768

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

Red List (low evidence)

Webb et al. (2017) reported 6 affected members of a 3-generation family with ?Townes-Brocks syndrome-2, identified heterozygosity for a nonsense mutation in the DACT1 gene that segregated with disease. Clinical features include imperforate anus, rectovaginal fistula, crossed fused renal ectopia, vesicoureteral reflux, unilateral microtia, overfolded helices and cupped ears. One family member (proband's mother) with scoliosis and spina bifida occulta. Neural tube defects reported in a study of human fetuses (PMID: 22610794) and a mouse model (PMID: 19701191). Listed in Decipher v10.0 for an individual with abnormalities of (i) head or neck (ii) nervous system (iii) skeletal system. Unlike the gene SALL1 that causes Townes-Brocks syndrome 1, there is no information specifically relating to DACT1 with radial dysplasia, as these were not observed in the family with ?Townes-Brocks syndrome 2 (PMID: 28054444).
Sources: NHS GMS

Created: 22 Jul 2020, 6:47 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Townes-Brocks syndrome 2 (OMIM #617466)

Publications

• PMID: 28054444
• 22610794
• 19701191

I don't know

Comment when marking as ready: Changed to Red after review against GEL gene-disease assessment.

Created: 16 Jan 2020, 6:01 a.m. | Last Modified: 16 Jan 2020, 6:01 a.m.

Panel Version: 0.57

Single multigenerational family with a heterozygous variant in this gene and features of TBS including CAKUT.
Sources: Expert list

Created: 28 Nov 2019, 5:28 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Townes-Brocks syndrome 2, MIM#617466

Publications

• 28054444