Skeletal dysplasia
Gene: NIN
Only two families reported in the literature with slightly different skeletal phenotypes. Furthermore, in the second family another homozygous variant also segregated with the disease. Also note these papers date from 2012/13 and no further evidence for gene-disease association has been published, which raises further concerns.Created: 19 Jul 2019, 2:43 a.m. | Last Modified: 19 Jul 2019, 2:43 a.m.
Panel Version: 1.192
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
not listed in nosology paper, but cases have severe pre- and postnatal growth retardation. Only 2 cases reported?; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Seckel syndrome 7 614851
Publications
Comment on list classification: Changing rating from green to red, in light of Zornitza Stark's red review. Evidence is not strong.Created: 9 Sep 2019, 10:29 p.m. | Last Modified: 9 Sep 2019, 10:29 p.m.
Panel Version: 1.201
PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S). The p.N1709S is a novel variant that is not present in Single Nucleotide Polymorphism database, 1000 Genomes pilot data, or the NHLBI exome variant server. The p.Q1222R was present only in the 1000 Genomes pilot data with an overall minor allele frequency of 0.001 (0.005 in the Americas subcohort). In patient derived primary dermal fibroblasts, the compound heterozygous NIN defects did not disrupt Ninein expression or localization or obviously affect mitotic functions. But zebrafish nin morphilino knockdowns include phenotypes such as reduced growth and altered patterning of the skull, consistent with general phenotypic characteristics of MPD.
PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype. The NIN variant is classified as a VUS in OMIM.Created: 7 May 2019, 9:42 p.m. | Last Modified: 17 Jul 2019, 2:25 p.m.
Panel Version: 1.192
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: NIN; Initial rating suggestion: amberCreated: 6 Mar 2019, 11:36 a.m.
Comment when marking as ready: At least three variants reported in this phenotypeCreated: 13 Jul 2016, 9:02 a.m.
Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)Created: 21 Jun 2016, 12:59 p.m.
Tier 1Created: 17 Jun 2016, 8:06 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Seckel syndrome 7 614851; Grosch M et al. Identification of a Ninein (NIN) mutation in a family with spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type)-like phenotype.Matrix Biol. 2013 Oct-Nov, 32(7-8):387-92.
Variants in this GENE are reported as part of current diagnostic practice
Gene: nin has been classified as Red List (Low Evidence).
Added phenotypes Seckel syndrome 7 614851 for gene: NIN Publications for gene NIN were changed from 23665482; 22933543 to 22933543; 23665482
Source NHS GMS was added to NIN. Rating Changed from Green List (high evidence) to Green List (high evidence)
Promoted to version 1 9th August 2016
Mode of inheritance for NIN was changed to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
Publications for NIN were set to 23665482; 22933543
Phenotypes for NIN were set to Seckel syndrome 7 614851
Publications for NIN were set to 23665482
Phenotypes for NIN were set to Seckel syndrome 7 614851; Grosch M et al. Identification of a Ninein (NIN) mutation in a family with spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type)-like phenotype.Matrix Biol. 2013 Oct-Nov, 32(7-8):387-92.
This gene has been classified as Green List (High Evidence).
NIN was created by sleigh
NIN was added to Unexplained skeletal dysplasiapanel. Sources: