Osteogenesis imperfectaGene: NUDT6
Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to rate this gene amber until there is more evidence for an association.
Created: 11 Jun 2019, 3 p.m.
This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: NUDT6; Suggested initial gene rating: amber
Created: 3 Apr 2019, 4:08 p.m.
PubMed search did not find any other reports of NUDT6 in association with an Osteogenesis imperfecta phenotype.
Created: 2 Apr 2019, 12:15 p.m.
Not associated with any disease phenotype in OMIM or Gene2Phenotype.
The publication citation from Duncan Baker of "Essawi et al A homozygous missense variant in NUDT6 is responsible for an autosomal recessive form of osteogenesis imperfecta" refers to a presentation given at the American Society of Human Genetics (ASHG 2018) conference. The abstract is available here http://www.ashg.org/meetings/documents/2018-platform-plenary-abstracts.pdf.
The abstract reports a consanguineous Palestinian family with three affected individuals who were clinically diagnosed as OI patients. No likely causal variants found in known recessive OI genes. Exome sequencing of the proband DNA revealed a novel homozygous missense variant (NM_007083: c.308G>T, NP_009014: p.Arg103Leu) in exon 2 of the NUDT6 gene. The variant segregated with the disease in the family (6 non-affected family members were either heterozygous carriers or non-carriers). NUDT6 is an expression regulator for the FGF2 gene. Functional studies show that NUDT6 was down-regulated in the proband's dermal fibroblasts and FGF2 was upregulated (RT-qPCR). Overexpression of the wild type and mutant NUDT6 gene in different cell lines showed significantly decreased levels of mutant NUDT6 RNA expression.
Created: 2 Apr 2019, 11:05 a.m.
Request from Dr Meena Balasubramian - plausible to cause bone fragility, add to panel if possible
Created: 3 Apr 2019, 4:14 p.m.
New gene, one report linking to OI phenotype.
Sources: Expert list
Created: 25 Jan 2019, 11:44 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
recurrent fractures, accompanied with other skeletal manifestations including short-limb dwarfism, mild frontal bossing, bowing of legs and scoliosis.
Gene: nudt6 has been classified as Amber List (Moderate Evidence).
Source NHS GMS was added to NUDT6. Rating Changed from No List (delete) to Red List (low evidence)
gene: NUDT6 was added gene: NUDT6 was added to Osteogenesis imperfecta. Sources: Expert list Mode of inheritance for gene: NUDT6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUDT6 were set to Essawi et al A homozygous missense variant in NUDT6 is responsible for an autosomal recessive form of osteogenesis imperfecta. Phenotypes for gene: NUDT6 were set to recurrent fractures, accompanied with other skeletal manifestations including short-limb dwarfism, mild frontal bossing, bowing of legs and scoliosis. Review for gene: NUDT6 was set to AMBER