TUB – Retinitis Pigmentosa

A homozygous missense variant in TUB has been identified as a probable cause of autosomal recessive retinitis pigmentosa. In a consanguineous Chinese family, whole exome sequencing revealed a novel homozygous NM_177972.3:c.1213A>G (p.Asn405Asp) variant that co-segregated with disease in the pedigree and was absent from 118 ethnically matched controls (Single proband; absent in controls) ([PMID:36650547]). No other pathogenic TUB variants were reported in 159 unrelated arRP, 114 simplex RP, or 21 LCA patients in a large mutation screen ([PMID:16643894]), indicating limited recurrence.

Functional modeling in Tub-deficient mice demonstrates photoreceptor apoptosis and progressive retinal degeneration, recapitulating key features of human RP and supporting a loss-of-function mechanism ([PMID:10629044]). These data, combined with evolutionary conservation of Asn405 and absence of the variant from population databases, establish a limited but credible gene–disease association for TUB in RP.

References

• BMC medical genomics • 2023 • A novel homozygous TUB mutation associated with autosomal recessive retinitis pigmentosa in a consanguineous Chinese family. PMID:36650547
• Experimental eye research • 2006 • Mutation screen of the TUB gene in patients with retinitis pigmentosa and Leber congenital amaurosis. PMID:16643894
• Molecular and cellular biology • 2000 • Targeted deletion of the tub mouse obesity gene reveals that tubby is a loss-of-function mutation. PMID:10629044

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