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| Clefting v7.3 | LOXL3 | Ida Ertmanska changed review comment from: Comment on list classification: There are now 8 individuals from 4 unrelated families with biallelic LOXL3 variants and variable clinical features consistent with Stickler syndrome, including cleft palate in 2 unrelated families. A mouse model with a knock in missense variant in LOXL3 recapitulated Stickler syndrome features, including clefting. Hence, this gene should be promoted to Green at the next update.; to: Comment on list classification: There are now 8 individuals from 4 unrelated families with biallelic LOXL3 variants and variable clinical features consistent with Stickler syndrome, including cleft palate in 4 individuals from 2 unrelated families. Another unrelated individual presented with a high-arched palate. A mouse model with a knock in missense variant in LOXL3 recapitulated Stickler syndrome features, including clefting. Hence, this gene should be promoted to Green at the next update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting v7.3 | LOXL3 | Ida Ertmanska Classified gene: LOXL3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting v7.3 | LOXL3 | Ida Ertmanska Added comment: Comment on list classification: There are now 8 individuals from 4 unrelated families with biallelic LOXL3 variants and variable clinical features consistent with Stickler syndrome, including cleft palate in 2 unrelated families. A mouse model with a knock in missense variant in LOXL3 recapitulated Stickler syndrome features, including clefting. Hence, this gene should be promoted to Green at the next update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting v7.3 | LOXL3 | Ida Ertmanska Gene: loxl3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting v7.2 | LOXL3 | Ida Ertmanska Tag Q2_26_promote_green tag was added to gene: LOXL3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting v7.2 | LOXL3 |
Ida Ertmanska gene: LOXL3 was added gene: LOXL3 was added to Clefting. Sources: Literature Mode of inheritance for gene: LOXL3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LOXL3 were set to 25663169; 30362103; 36610533; 36917121; 38957076; 41052910 Phenotypes for gene: LOXL3 were set to Myopia 28, autosomal recessive, OMIM:619781; Stickler syndrome, MONDO:0019354 Review for gene: LOXL3 was set to GREEN Added comment: PMID: 41052910 Sanchez et al., 2026 3 sisters with biallelic LOXL3 variants and Stickler Syndrome. Comp het for c.1735C>T, p.Arg579* and c.956G>A, p.Arg319Gln in LOXL3 - targeted NGS panel. Parents are healthy carriers of one LOXL3 variant each. Shared phenotype: skeletal anomalies in feet and hands, cleft palate, high myopia, bilateral conductive hearing loss (2/3). PMID: 38957076 Klejnotowska et al., 2024 4yo boy with reduced visual acuity 6/30 in both eyes, bilateral vitreous syneresis, foveal hypoplasia and bilateral high myopia (-8.50D). A skeletal survey showed mild spondylo-epi-metaphyseal dysplasia. Normal hearing. WES revealed a homozygous LOXL3 variant c.1448_1449del, p.(Thr483Argfs*13), inherited through paternal UPiD of chromosome 2. PMID: 36917121 Jiang et al., 2023 9 unrelated Chinese patients with LOXL3 variants and early-onset extreme high myopia - main and consistent feature across the cohort. No significant skeletal abnormalities, midface development, palate malformation was observed in these nine patients; auditory assessment normal where available. Authors hypothesise that biallelic missense variants result in Stickler syndrome, while truncating variants yield isolated high myopia - this is not very consistent, though. PMID: 30362103 Chan et al., 2019 Report of a child and his father who had clinical features consistent with Stickler syndrome and found to have a homozygous novel mutation c.1036C>T (p.Arg346Trp) in LOXL3. Clinical features: high myopia, short stature, retinal changes, high-arched palate (son only). No hearing loss. PMID: 25663169 Alzahrani et al., 2015 Saudi family with AR Stickler syndrome. Parents are second cousins. Index patient: 16yo boy with cleft palate, micro/retrognathia, non-progressive myopia (-10.00 D) with chorioretinal lattice degeneration, mild conductive hearing loss. 8yo sister has similar presentation, with myopia of -13.00 D and normal hearing. Both had normal development. Homozygous LOXL3 c.2027G>T, p.Cys676Phe detected in the sibs (exome seq + autozygosity filtering). Functional evidence: PMID: 36610533 Liu et al., 2023 - a mouse model of Stickler syndrome was made by inducing a LOXL3 mutation (c.2027G>A, p.Cys676Tyr) using CRISPR/Cas9. The Loxl3 mutant mice exhibited perinatal death, spinal deformity, cleft palate, skeletal dysplasia and progressive visual degeneration. Sources: Literature |
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