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Congenital fibrosis of the extraocular muscles v2.7 ZFHX4 Ida Ertmanska Tag Q3_26_expert_review was removed from gene: ZFHX4.
Tag Q3_26_NHS_review tag was added to gene: ZFHX4.
Congenital fibrosis of the extraocular muscles v2.7 ZFHX4 Ida Ertmanska Tag Q3_26_expert_review tag was added to gene: ZFHX4.
Tag Q3_26_promote_green tag was added to gene: ZFHX4.
Congenital fibrosis of the extraocular muscles v2.7 ZFHX4 Ida Ertmanska Phenotypes for gene: ZFHX4 were changed from Isolated congenital ptosis to congenital ptosis, MONDO:0008340
Congenital fibrosis of the extraocular muscles v2.6 ZFHX4 Ida Ertmanska Publications for gene: ZFHX4 were set to PMID: 41524020; 11935336; 32962661
Congenital fibrosis of the extraocular muscles v2.5 ZFHX4 Ida Ertmanska Classified gene: ZFHX4 as Amber List (moderate evidence)
Congenital fibrosis of the extraocular muscles v2.5 ZFHX4 Ida Ertmanska Added comment: Comment on list classification: There are more than 3 unrelated patients reported in literature with heterozygous ZFHX4 variants and isolated congenital ptosis. Hence, this gene can be promoted to Green at the next update.
Congenital fibrosis of the extraocular muscles v2.5 ZFHX4 Ida Ertmanska Gene: zfhx4 has been classified as Amber List (Moderate Evidence).
Congenital fibrosis of the extraocular muscles v2.4 ZFHX4 Ida Ertmanska edited their review of gene: ZFHX4: Changed publications to: 41524020, 32962661, 17987257, 11935336
Congenital fibrosis of the extraocular muscles v2.4 ZFHX4 Ida Ertmanska changed review comment from: PMID: 41524020 Zhang et al., 2026
Cohort of patients with isolated congenital ptosis. Seq method: WES. Three novel heterozygous variants in ZFHX4, c.5145C>A (p.N1715K), c.10382C>T (p.A3461V), and c.10795G>A (p.A3599T), were identified in three patients of Han Chinese origin.

PMID: 32962661 Adhikari et al., 2020
Report of a Nepalese proband with congenital ptosis and a c.12411G>T, p.Leu4137Phe variant in exon 12 of ZFHX4.
Same variant reported in a Japanese kindred with hereditary congenital blepharoptosis (PMID: 17987257, Nakashima et al., 2008).

This gene is not yet associated with a disease entity in OMIM. ZFHX4 association with AD syndromic complex neurodevelopmental disorder was classified as Strong in ClinGen in December 2025 (Intellectual Disability and Autism GCEP).; to: PMID: 41524020 Zhang et al., 2026
Cohort of patients with isolated congenital ptosis. Seq method: WES. Three novel heterozygous variants in ZFHX4, c.5145C>A (p.N1715K), c.10382C>T (p.A3461V), and c.10795G>A (p.A3599T), were identified in three patients of Han Chinese origin.

PMID: 32962661 Adhikari et al., 2020
Report of a Nepalese proband with congenital ptosis and a c.12411G>T, p.Leu4137Phe variant in exon 12 of ZFHX4.
Same variant reported in a Japanese kindred with hereditary congenital blepharoptosis (PMID: 17987257, Nakashima et al., 2008).

PMID: 11935336 McMullan et al., 2002
Report of a patient with congenital bilateral isolated ptosis and a de novo balanced translocation 46,XY,t(1;8)(p34.3;q21.12). The 1p breakpoint does not disrupt a coding sequence, whereas the chromosome 8 breakpoint disrupts the ZFHX4 gene.

This gene is not yet associated with a disease entity in OMIM. ZFHX4 association with AD syndromic complex neurodevelopmental disorder was classified as Strong in ClinGen in December 2025 (Intellectual Disability and Autism GCEP).
Congenital fibrosis of the extraocular muscles v2.4 ZFHX4 Ida Ertmanska reviewed gene: ZFHX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 41524020, 32962661, 17987257; Phenotypes: congenital ptosis, MONDO:0008340; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital fibrosis of the extraocular muscles v2.4 ZFHX4 Nicky Cronbach gene: ZFHX4 was added
gene: ZFHX4 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX4 were set to PMID: 41524020; 11935336; 32962661
Phenotypes for gene: ZFHX4 were set to Isolated congenital ptosis
Penetrance for gene: ZFHX4 were set to unknown
Review for gene: ZFHX4 was set to GREEN
Added comment: Multiple unrelated cases of isolated congenital ptosis reported. Three unrelated Han-Chinese patients (PMID 41524020) and one Nepalese patient (32962661) with missense variants in ZFHX4, and one case (unspecified ethnicity) related to a translocation disrupting ZFHX4.
Sources: Literature