Skeletal dysplasia
Gene: NMNAT1
Comment on list classification: As two of the three reported families were distantly related, this gene should only be rated AMBER with the current evidence. However, 'watchlist' tag was added to review the rating in light of new evidence in the future.Created: 25 May 2023, 7 p.m. | Last Modified: 25 May 2023, 7 p.m.
Panel Version: 4.3
The 'cnv' tag was added as two of the reported cases harboured duplication variants in homozygous state and the third case harboured duplication variant together with a splicing variant.Created: 25 May 2023, 6:58 p.m. | Last Modified: 25 May 2023, 6:58 p.m.
Panel Version: 4.2
PMID:32533184 reported two distantly related families homozygous for 7.4-kb duplication involving the last 2 exons of the NMNAT1 gene (chr1:10,036,359-10,043,727, GRCh37).
PMID:33668384 reported a 2-year-old girl compound heterozygous for the duplication and with a splicing variant (c.439+5G>T).
These patients presented with a severe form of spondylo-epiphyseal dysplasia, sensorineural hearing loss, intellectual disability, Leber congenital amaurosis and several brain abnormalities.
This gene has been associated with relevant phenotypes in OMIM (MIM #619260).Created: 25 May 2023, 6:55 p.m. | Last Modified: 25 May 2023, 6:55 p.m.
Panel Version: 4.2
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis, OMIM:619260
Publications
The association with LCA is well established.
New report of a syndromic LCA disorder and note also unusual variant type. Three families, but two are distantly related (shared haplotype). The affected children in those two families were homozygous for 7.4-kb duplication involving the last 2 exons of the NMNAT1 gene, spanning the beginning of intron 3 to the middle of the 3-prime UTR (chr1:10,036,359-10,043,727, GRCh37). The third affected individual was compound het for the duplication and a splicing variant.
Sources: LiteratureCreated: 17 Apr 2021, 7:39 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260
Publications
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: NMNAT1 were set to 32533184; 33668384
Publications for gene: NMNAT1 were set to 32533184; 33668384
Publications for gene: NMNAT1 were set to 32533184
Gene: nmnat1 has been classified as Amber List (Moderate Evidence).
Tag watchlist tag was added to gene: NMNAT1. Tag cnv tag was added to gene: NMNAT1.
gene: NMNAT1 was added gene: NMNAT1 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: NMNAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NMNAT1 were set to 32533184 Phenotypes for gene: NMNAT1 were set to Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260 Review for gene: NMNAT1 was set to GREEN gene: NMNAT1 was marked as current diagnostic