CAKUT
Gene: BMP4Kept rating as Amber following agreement from Helen Brittain, Genomics England Clinical Team: evidence is borderline and further cases or supportive evidence is needed to be confident of a causal link. Rated Amber but can be re-assessed by GLH groups at a future date.Created: 21 Apr 2020, 3:31 p.m. | Last Modified: 4 Jun 2020, 3:08 p.m.
Panel Version: 1.151
Comment on list classification: Updated rating from Red to Amber based on a number of papers linking BMP4 variants and renal phenotypes. Penetrance isn't complete (PMID:18305125), and phenotype is variable, even within families (PMID:30568244). However a mouse model supports a renal phenotype, and functional evidence shows expression in renal tissues. Therefore rated Amber awaiting further clinical review.Created: 30 Mar 2020, 4:21 p.m. | Last Modified: 30 Mar 2020, 4:21 p.m.
Panel Version: 1.47
Comment on phenotypes: Not currently associated with a renal phenotype in OMIM or Gene2Phenotype.Created: 30 Mar 2020, 4:18 p.m. | Last Modified: 30 Mar 2020, 4:18 p.m.
Panel Version: 1.46
Additional mouse model in PMID:18233958 where mutant mice result in uropathies resembling human CAKUT.Created: 30 Mar 2020, 4:15 p.m. | Last Modified: 30 Mar 2020, 4:15 p.m.
Panel Version: 1.43
PMID:30568244 (Nixon et al., 2019) investigate a BMP4 variant ( c. 130G>T, p.(Gly44Ter) with segregated in a family with Stickler syndrome. One male (age 20) also had congenital renal dysplasia. No other family members reported kidney disease.Created: 30 Mar 2020, 4:15 p.m. | Last Modified: 30 Mar 2020, 4:15 p.m.
Panel Version: 1.43
PMID:18305125 (Weber et al., 2008) report 3 BMP4 variants in 5 unrelated CAKUT patients (Ser91Cys, heterozygous in patients 6 and 7; Thr116Ser, heterozygous in patient 8; Asn150Lys, heterozygous in patient 9 and homozygous in patient 10). Patients were from Poland, Germany and Turkey. All five affected patients presented with a spectrum of renal maldevelopment, ranging from kidney agenesis to hypoplasia and dysplasia (with or without
cysts). The father of patient 7 also had the variant but had normal renal ultrasound. The inheritance may be polygenic: the authors show expression of BMP4 in human renal tissue. PMID:19685083 (Tabatabaeifar et al., 2009) report functional evidence for these three missense mutations, and provide in vitro functional evidence in human cell lines that BMP4 mRNA is reduced in the mutants.Created: 30 Mar 2020, 3:39 p.m. | Last Modified: 30 Mar 2020, 3:42 p.m.
Panel Version: 1.43
PMID:23641053 (Kaku et al., 2013). Indirect Animal study. Authors studied renal expression and phenotype of Isl1 in mice. Lack of Isl1 reduced the expression of mouse Bmp4.Created: 30 Mar 2020, 2:05 p.m. | Last Modified: 30 Mar 2020, 2:05 p.m.
Panel Version: 1.43
PMID:24131739 (Reis et al. 2014) performed an association study, analysing 3 BMP4 SNPs (rs17563, rs2071047, and rs762642) in 457 Brazilian individuals to study the link between BMP4 and CAKUT.Created: 30 Mar 2020, 2:04 p.m. | Last Modified: 30 Mar 2020, 2:04 p.m.
Panel Version: 1.43
At least 6 patients reported with variants in this gene and CAKUT; mouse model supports pathogenicity.Created: 16 Jan 2020, 3:14 a.m. | Last Modified: 16 Jan 2020, 3:14 a.m.
Panel Version: 1.41
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
CAKUT
Publications
Gene: bmp4 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: BMP4 were changed from to CAKUT; renal maldevelopment; congenital renal dysplasia; Congenital Anomaly of the Kidneys and Urinary Tract
Publications for gene: BMP4 were set to
Mode of inheritance for gene: BMP4 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
This gene has been classified as Red List (Low Evidence).
BMP4 was added to Congenital Anomaly of the Kidneys and Urinary Tract (CAKUT)panel. Sources: Expert list