Arthrogryposis

Gene: NEK9

The rating of this gene has been updated following NHS Genomic Medicine Service approval

Created: 3 Mar 2022, 3:49 p.m. | Last Modified: 3 Mar 2022, 3:49 p.m.

Panel Version: 3.150

Green List (high evidence)

NEK9 is associated with relevant phenotypes in OMIM (MIM# 614262 and 617022) but currently is not in Gene2Phenotype.

Created: 18 Jan 2021, 3:10 p.m. | Last Modified: 18 Jan 2021, 3:10 p.m.

Panel Version: 3.46

Comment on list classification: With addition of the recent report, there are now at least 3 unrelated families presenting arthrogryposis and different biallelic variants in this gene. This now reaches threshold for inclusion, and therefore NEK9 should be promoted to Green at the next GMS panel update (added 'for-review' tag)

Created: 18 Jan 2021, 3:05 p.m. | Last Modified: 18 Jan 2021, 3:05 p.m.

Panel Version: 3.45

Deden et al. 2020 (PMID: 32333414) report a further family with two consecutive prenatal presentations with compound heterozygous NEK9 variants. Both fetuses had arthrogryposis.

Both variants were reported as VUS when detected in the first fetus, which initially presented with 'short long bones, bowed femur, micrognathia, talipes and deviated hand' but re-evaluated after the phenotype progressed to arthrogryposis and then the next pregnancy showed the same ultrasound abnormalities and the same compound het variants. At this point the authors felt this represented a conclusive diagnosis.

Created: 18 Jan 2021, 3:01 p.m. | Last Modified: 18 Jan 2021, 3:01 p.m.

Panel Version: 3.44

Comment on list classification: Upgraded from Red to Amber in line with the recent review by Rhiannon Mellis (GOSH). Additional cases/clinical evidence required before inclusion on a diagnostic panel.

Created: 2 Dec 2020, 5:08 p.m. | Last Modified: 2 Dec 2020, 5:08 p.m.

Panel Version: 3.21

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 26908619
• 21271645
• 26633546
• 32333414

I don't know

Casey et al 2016 report 4 affected fetuses in two Irish Traveller families: phenotype = fetal akinesia, shortening of all long bones, multiple contractures, rib anomalies, thoracic dysplasia, pulmonary hypoplasia. The two families are thought to be distantly related to one another.

In addition to the previously reported 3 individuals from one Saudi family, this likely represents two affected families so probably still not enough evidence for Green rating until more cases reported.

Created: 6 Oct 2020, 3:33 p.m. | Last Modified: 6 Oct 2020, 3:33 p.m.

Panel Version: 3.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Lethal congenital contracture syndrome 10

Publications

• PMID: 26908619

Red List (low evidence)

Only reported in three individuals from one family

Created: 5 Jan 2017, 10:48 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Arthrogryposis, Perthes disease, and upward gaze palsy 614262

Publications

• 26633546
• 21271645