Unexplained young onset end-stage renal disease - additional genes

Gene: ANOS1

Green List (high evidence)

This gene has been added to this panel with green rating as it was present in R257 Unexplained young onset end-stage renal disease panel (v5.1) with the same rating before it was made a super panel.

Created: 25 Sep 2024, 9:36 p.m. | Last Modified: 25 Sep 2024, 9:36 p.m.

Panel Version: 0.65

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

I don't know

Comment on mode of inheritance: Changing mode of inheritance to X-LINKED: hemizygous mutation in males, biallelic mutations in females as monoallelic females do not present with a disease phenotype.

Created: 23 Oct 2019, 10:53 a.m. | Last Modified: 23 Oct 2019, 10:53 a.m.

Panel Version: 0.45

PMID:9719154 Duke et al 1998 - reports overt renal failure in one adult with a contiguous deletion involving KAL1/ANOS1, and evidence of impaired renal function in a second adult with a clinical diagnosis of Kallmann syndrome. Both had unilateral renal agenesis.

PMID: 17603054 - Georgopoulos et al 2007 - report renal dysgenesis in 2 out of 16 male KS patients. One had two missense mutations in the KAL1 gene, the other had deletion of exons 5–10 of the KAL1 gene and a complete deletion of the steroid sulphatase (STS) gene which accounts for the X-linked ichthyosis seen in that patient.

PMID: 23533228 - Costa-Barbosa et al 2014 - report a cohort of 38 Kallman syndrome patients with rare variants in KAL1. 3/17 of them (where data was available) had renal agenesis.

PMID: 25597551 - Xu et al 2015 - report 2 Chinese brothers with KS and X-linked ichthyosis. The phenotypes of the patients were characterised by bilateral cryptorchidism, unilateral renal agenesis in one patient but normal kidney development in another. The two affected siblings had the same novel deletion at Xp22.3 including exons 9-14 of KAL1 gene and entire STS gene.

Note on MOI - PMID: 11297579 - Oliveira et al 2001 - report that "Genetically proven female carriers of KAL mutations in 3 families all had normal pubertal development, with regular menstrual cycles and normal olfaction". They also evaluated three families in which anosmic women gave birth to sons with KS, and none had any mutation in the coding sequence of the KAL gene.

Therefore I think the MOI should be X-LINKED: hemizygous mutation in males, biallelic mutations in females as monoallelic females do not appear to present with the relevant phenotype.

Created: 23 Oct 2019, 10:52 a.m. | Last Modified: 8 Nov 2019, 2:18 p.m.

Panel Version: 0.56

Gene imported from the 'Renal and urinary tract disorders' panel v1.8 with a rating of Green

Created: 9 Apr 2019, 11:17 a.m.

Red List (low evidence)

Although unilateral renal agenesis is seen in a subset of individuals with Kallmann syndrome due to variants in ANOS1, there is little evidence that this is associated with impaired renal function in childhood. PMID:9719154 reports overt renal failure in one adult with a contiguous deletion involving KAL1, and evidence of impaired renal function in a second adult with a clinical diagnosis of Kallmann syndrome. Both had unilateral renal agenesis.

Created: 3 Dec 2018, 7:54 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1)

Publications

• 11531922
• 9719154

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

added new-gene-name tag, new symbol is ANOS1

Created: 27 Feb 2017, 1:55 p.m.

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P. Numerous variants reported

Created: 4 Aug 2016, 2:03 p.m.

Comment on list classification: Gene added by reviewer. The new HGNC-approved symbol for this gene is ANOS1 (for genome build 38).

Created: 22 Apr 2016, 12:22 p.m.

Comment on list classification: Two reviewers agree this gene should be green.

Created: 22 Apr 2016, 12:04 p.m.

Green List (high evidence)

Numerous publications show that X-linked Kallman syndrome (i.e. KAL1 mutant) hemizygous males have a 20-30% risk of being born with a single kidney.

Created: 22 Apr 2016, 11:43 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)