Limb disorders

Gene: KYNU

Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.

Created: 19 Oct 2020, 2:44 p.m. | Last Modified: 19 Oct 2020, 2:44 p.m.

Panel Version: 2.15

Green List (high evidence)

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

Created: 5 Mar 2022, 8:17 p.m. | Last Modified: 5 Mar 2022, 8:17 p.m.

Panel Version: 2.67

Comment on list classification: Changing the rating from red to green as 3 unrelated cases have been reported with a distinct hand hyperphalangism phenotype and biallelic or compound heterozygous variants, and segregation as expected in the family in 2 cases (3rd could not be established).

Created: 15 Jun 2020, 8:34 a.m. | Last Modified: 15 Jun 2020, 8:34 a.m.

Panel Version: 2.7

KYNU is associated with Vertebral, cardiac, renal, and limb defects syndrome 2 #617661 (AR) in OMIM.

PMID: 31923704 Ehmke et al 2020 - report 3 unrelated individuals with a ballelic or compound het (a deletion of axons 1-8 and a missense variant) in KYNU and a multisystemic syndrome with hand hyperphalangism resembling Catel-Manzke syndrome. Other features included heart defects and developmental delay (mild in 2 cases) and mild vertebral defects. Microretrognathia was observed in 2 patients consistent with Catel-Manzke syndrome. Two affected individuals tested had elevated urine xanthurenic acid.

PMID: 28792876 Shi et al 2017 - report 2 families where the proband is homozygous or compound heterozygous for loss of function variants in KUNU. The hyperphalgnism described by Ehmke et al was NOT seen, although one patient had talipes, syndactyly and rhizomelia and the other had shortened long bones. Both had cardiac, renal and defects in vertebral segmentation.
Sources: Literature

Created: 15 Jun 2020, 8:32 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Vertebral, cardiac, renal, and limb defects syndrome 2, 617661; hand hyperphalangism

Publications

• 31923704