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Skeletal dysplasia v2.180 GZF1 Eleanor Williams Tag for-review was removed from gene: GZF1.
Skeletal dysplasia v2.176 GZF1 Eleanor Williams commented on gene: GZF1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.175 GZF1 Eleanor Williams Source Expert Review Green was added to GZF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v2.81 GZF1 Ivone Leong Tag for-review tag was added to gene: GZF1.
Skeletal dysplasia v2.70 GZF1 Eleanor Williams Phenotypes for gene: GZF1 were changed from Larsen syndrome to Larsen syndrome; joint laxity, short stature, and myopia OMIM:617662; joint laxity, short stature, and myopia MONDO:0060556
Skeletal dysplasia v2.69 GZF1 Eleanor Williams Publications for gene: GZF1 were set to 28475863
Skeletal dysplasia v2.68 GZF1 Eleanor Williams Classified gene: GZF1 as Amber List (moderate evidence)
Skeletal dysplasia v2.68 GZF1 Eleanor Williams Added comment: Comment on list classification: Leaving the rating as amber for now, but with a recommendation of green following GMS review.
Skeletal dysplasia v2.68 GZF1 Eleanor Williams Gene: gzf1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.67 GZF1 Eleanor Williams edited their review of gene: GZF1: Added comment: Associated with Joint laxity, short stature, and myopia #617662 (AR) in OMIM.

As reported by Zornitza Stark, PMID: 33009817 (Zeng et al 2020) reported two Chinese sisters who presented with severe myopia, scoliosis and hearing loss. Using WES they identified two compound heterozygous variants in GZF1 (c.397400del, p. Leu133fs; c.1474del, p. Met492fs). The parents were heterozygous carriers of the variants. Functional data showed decreased levels of HA‐tagged M492fs‐GZF1 protein and no HA-tagged L133fs‐GZF1 protein or the control vector. HA‐tagged M492fs‐GZF1 protein was also localized to the cytoplasm rather than the nuclei in which wild type protein was found.

This now brings the case number to 3.; Changed rating: GREEN; Changed publications: 33009817; Changed phenotypes: joint laxity, short stature, and myopia OMIM:617662, joint laxity, short stature, and myopia MONDO:0060556; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.21 GZF1 Zornitza Stark reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662, Larsen-like syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v1.202 GZF1 Eleanor Williams Classified gene: GZF1 as Amber List (moderate evidence)
Skeletal dysplasia v1.202 GZF1 Eleanor Williams Added comment: Comment on list classification: Demoting from green to amber. 2 cases plus functional data, but the functional data does not strongly support a skeletal phenotype.
Skeletal dysplasia v1.202 GZF1 Eleanor Williams Gene: gzf1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.192 GZF1 Eleanor Williams Classified gene: GZF1 as Green List (high evidence)
Skeletal dysplasia v1.192 GZF1 Eleanor Williams Gene: gzf1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Deleted their comment
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Classified gene: GZF1 as Amber List (moderate evidence)
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Added comment: Comment on list classification: Demoting from Green to Amber as a result of expert review. Only 2 cases although there is some functional evidence supporting the role of this protein in the disease.
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Gene: gzf1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.166 GZF1 Eleanor Williams commented on gene: GZF1: Associated with Joint laxity, short stature, and myopia (#617662) in OMIM and with LARSEN SYNDROME (probable) in Gene2Phenotype. Generalized joint laxity is listed as a phenotype for Larsen syndrome 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. A homozygous truncating variant in GZF1 was identified (c.865G>T (pGlu289∗). Family 2 - another multiplex consanguineous family affected by severe myopia, retinal detachment, and milder skeletal involvement (generalized joint laxity) 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.
Skeletal dysplasia v1.153 GZF1 Eleanor Williams Added phenotypes Larsen syndrome for gene: GZF1
Skeletal dysplasia v1.147 GZF1 Tracy Lester reviewed gene: GZF1: Rating: AMBER; Mode of pathogenicity: ; Publications: 28475863; Phenotypes: Larsen syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.146 GZF1 Eleanor Williams reviewed gene: GZF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.145 GZF1 Eleanor Williams Source NHS GMS was added to GZF1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia GZF1 Sarah Leigh classified GZF1 as green
Skeletal dysplasia GZF1 Sarah Leigh added GZF1 to panel
Skeletal dysplasia GZF1 Sarah Leigh reviewed GZF1