Nephrocalcinosis or nephrolithiasis
Gene: MOCOS
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 7 Mar 2022, 11:21 p.m. | Last Modified: 7 Mar 2022, 11:21 p.m.
Panel Version: 2.32
Comment on list classification: Promoting from grey to amber, with a recommendation for green rating following GMS review. 2 cases where urolithiasis is part of the Xanthinuria type 2 phenotype. Additional evidence from animal models.Created: 19 Aug 2021, 11:33 a.m. | Last Modified: 19 Aug 2021, 11:33 a.m.
Panel Version: 2.24
Cases with MOCOS variants where urolithiasis is reported:
PMID:17368066 - Peretz et al 2007 - report 2 individuals both diagnosed with xanthinuria and with variants in MOCOS (HMCS). A Bedouin-Arab child presenting with urolithiasis was found to homozygous for a p.Arg776Cys variant, and an asymptomatic Jewish female originating from Italy was compound hetergozygous for this and a frameshift variant leading to a stop codon. Cosegregation of the homozygous mutant genotype with hypouricemia and hypouricosuria was demonstrated in the Bedouin family.
PMID: 34356852- Peretz et al 2021 - report on 3 families (F1, F3 and F8) thought to share a Yemenite-Jewish founder MOCOS variant (c.1046C>T, p.(T349I)) causing xanthinuria. Urolithiasis reported in some affected members in one of the families. Additionally an asymptomatic female from Germany with low levels of uric acid in the serum and urine was found to be compound het for variants in MOCOS. There was no history of urolithiasis.
PMID: 30758870 - Vail et al 2019 - report a goat with xanthine urolithiasis and a heterozygous XDH p.Leu128Pro variant and a homozygous MOCOS p.Asp303Gly variant thought to be potentially pathogenic.
PMID: 27919260 - Murgiano et al 2016 - large pedigree of Tyrolean Grey cattle with a history of kidney abnormalities and formation of uroliths. Using WGS a homozygous 1bp deletion in MOCOS was detected which affects both known transcripts.
Further cases but no urolithiasis reported:
PMID: 11302742 - Ichida et al 2001 - 2 unrelated Japanese patients diagnosed with xanthinuria type II in which the same homozygous nonsense variant (R419X) was identified in MOCOS (called HMCS in the publication). Patient 1 had hypouricemia and chronic renal failure due to polycystic kidney.
PMID:14624414 -Yamamoto et al 2003 - 43-year-old xanthinuric female with hypouricemia, A missense variant was found in MOCOS (called MCS in the publication).
PMID:25967871 - Zhou et al 2015 - 42 yo male with hypouricemia and mild albuminuria. WES identified a heterozygous nonsense variant in MCSU
PMID:32073534 - Tanev et al 2020 - patient with Juvenile Idiopathic Arthritis and Hereditary Xanthinuria - no genetic diagnosis. Urolithiasis not reported.Created: 19 Aug 2021, 11:21 a.m. | Last Modified: 19 Aug 2021, 11:21 a.m.
Panel Version: 2.21
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Xanthinuria, type II, OMIM:603592
This gene had not been previously included in this panel, but there is good evidence from several publications that recessive loss-of-function variants in MOCOS are associated with Xanthinuria type 2. There is also a good pathophysiologic basis: MOCOS encodes a necessary co-factor for the 2 enzymes that degrade Xanthine, XDH and AOX1.
Moreover, there are spontaneous animal models, with MOCOS variants identified in a goat (PMID 30758870) and Tyrolean grey cattle (PMID 27919260).
Sources: LiteratureCreated: 11 Aug 2021, 11:32 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Xanthinuria type II (MIM603592)
Publications
Tag Q3_21_rating was removed from gene: MOCOS. Tag Q3_21_NHS_review was removed from gene: MOCOS.
Source Expert Review Green was added to MOCOS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q3_21_NHS_review tag was added to gene: MOCOS.
Gene: mocos has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MOCOS were changed from Xanthinuria type II (MIM603592) to Xanthinuria, type II, OMIM:603592
Publications for gene: MOCOS were set to PMID: 11302742; 17368066; 14624414; 25967871; 34356852; 32073534; 30758870; 27919260
Tag Q3_21_rating tag was added to gene: MOCOS.
gene: MOCOS was added gene: MOCOS was added to Nephrocalcinosis or nephrolithiasis. Sources: Literature Mode of inheritance for gene: MOCOS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MOCOS were set to PMID: 11302742; 17368066; 14624414; 25967871; 34356852; 32073534; 30758870; 27919260 Phenotypes for gene: MOCOS were set to Xanthinuria type II (MIM603592) Penetrance for gene: MOCOS were set to Incomplete Review for gene: MOCOS was set to GREEN