Limb disordersGene: GZF1
Patel AJHG 100:831-6;2017
Created: 1 Aug 2019, 5:10 p.m. | Last Modified: 1 Aug 2019, 5:10 p.m.
Panel Version: 1.24
Comment on list classification: Keeping red. Genomics England clinical team note this is not a particularly limb-predominant phenotype, and is better suited to the skeletal dysplasia/Stickler syndrome panels.
Created: 26 Nov 2019, 12:20 a.m. | Last Modified: 26 Nov 2019, 12:20 a.m.
Panel Version: 1.123
Associated with Joint laxity, short stature, and myopia (#617662) in OMIM and Larsen syndrome (probable) in Gene2Phenotype.
PMID: 28475863 - Patel et al 2017 - 2 cases. Family 1 - a multiplex consanguineous Saudi family affected by severe and recurrent large joint dislocation and severe myopia. The index patient also had severe kyphoscoliosis. Both the index patient and her brother had short stature and bilateral talipes equinovarus deformity. A homozygous truncating variant in GZF1 was identified (c.865G>T (pGlu289∗). Family 2 - another multiplex consanguineous Saudi family affected by severe myopia, retinal detachment, and milder skeletal involvement (generalized joint laxity). 1 family member had bilateral talipes. A second homozygous truncating GZF1 variant was identified (c.1054dup (p.Thr352Asnfs∗50). Neither variant was present in 2,379 Saudi exomes or the Exome Aggregation Consortium (ExAC) Browser. In functional studies they found using immunofluorescence, strong localization of GZF1 in the developing mouse eye and, to a lesser extent, in the mesenchyme of the developing mouse limb buds. Using 3 patient-derived lymphoblastoid cell lines they found 1,095 genes to be dysregulated in affected individuals.
Created: 7 Aug 2019, 10:35 a.m. | Last Modified: 7 Aug 2019, 10:40 a.m.
Panel Version: 1.42
Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Created: 1 Aug 2019, 4:26 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Gene: gzf1 has been classified as Red List (Low Evidence).
Publications for gene: GZF1 were set to
Phenotypes for gene: GZF1 were changed from to Joint laxity, short stature, and myopia, 617662; Larsen syndrome
gene: GZF1 was added gene: GZF1 was added to Limb disorders. Sources: Expert list Mode of inheritance for gene: GZF1 was set to BIALLELIC, autosomal or pseudoautosomal