LOXL3 – Stickler syndrome

Autosomal recessive inheritance of LOXL3 variants has been demonstrated in two unrelated families with Stickler syndrome. In both families, affected individuals were homozygous for the missense variant c.1036C>T (p.Arg346Trp), confirmed by segregation analysis; in the second family the variant also segregated in an affected father under a pseudodominant pattern ([PMID:25663169]; [PMID:30362103]).

LOXL3 encodes a copper-dependent amine oxidase that catalyzes collagen crosslinking. A CRISPR/Cas9 Loxl3 mutant mouse recapitulates key Stickler-like features, including cleft palate, skeletal dysplasia and progressive retinal degeneration, supporting a loss-of-function mechanism ([PMID:36610533]). Biallelic LOXL3 variants should be considered in the diagnostic evaluation of autosomal recessive Stickler syndrome.

References

• Human genetics • 2015 • LOXL3, encoding lysyl oxidase-like 3, is mutated in a family with autosomal recessive Stickler syndrome. PMID:25663169
• Clinical genetics • 2019 • LOXL3 novel mutation causing a rare form of autosomal recessive Stickler syndrome. PMID:30362103
• Developmental biology • 2023 • Progressive degeneration of the retina in Loxl3 mutant mouse model of Stickler syndrome. PMID:36610533

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