Skeletal dysplasia

Gene: ZSWIM6

Green List (high evidence)

MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X) identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype.
MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp

Created: 29 Aug 2020, 8:31 a.m. | Last Modified: 10 Sep 2020, 11:54 p.m.

Panel Version: 0.4309

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, MIM# 617865; Acromelic frontonasal dysostosis, MIM# 603671

Publications

• 29198722
• 25105228
• 26706854

I don't know

Minimal reports to date. Acromelic frontonasal dysostosis considered as likely ciliopathy in one paper.

PMID: 25105228: 4 pts with AFND (Arg1163Trp)

PMID: 28213462; AFND caused by this gene was classified as "Likely ciliopathy"

PMID: 29198722; Reported 7 unrelated individuals with a recurrent truncating variant. This patients were "Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features". No functional studies performed but postulated to be dominant-negative.

Rated green in PanelApp UK - Rare multisystem ciliopathy disorders list
Sources: Expert Review

Created: 4 May 2020, 4:04 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Acromelic frontonasal dysostosis (MIM#603671)

Publications

• 25105228
• 28213462
• 29198722

Mode of pathogenicity
Other