IFT172 – short-rib thoracic dysplasia 9 (Mainzer-Saldino syndrome)

IFT172 encodes a core intraflagellar transport B (IFT-B) complex protein essential for cilium assembly and maintenance. Biallelic hypomorphic or null variants in IFT172 have been implicated in a spectrum of ciliopathies, notably Jeune asphyxiating thoracic dystrophy and isolated retinal degeneration (PMID:25168386). Although IFT172 is a candidate gene for short-rib thoracic dysplasia 9 (Mainzer-Saldino syndrome, MONDO:0009964), to date no affected individuals with confirmed IFT172 variants meeting diagnostic criteria for SRTD9 have been reported, and autosomal recessive inheritance is inferred from loss-of-function alleles. Functional modeling in zebrafish demonstrates that ift172 deficiency leads to shortened body axis, craniofacial anomalies, and skeletal defects analogous to human thoracic dysplasia, supporting a pathogenic mechanism of haploinsufficiency or hypomorphism in skeletal ciliopathies (PMID:36533556). Additional diagnostic case reports and segregation data are required to establish a definitive gene-disease relationship.

Key Take-home: Biallelic IFT172 variants are biologically plausible for autosomal recessive short-rib thoracic dysplasia 9, but current evidence is limited and further clinical validation is needed.

References

• Human molecular genetics • 2015 • Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome PMID:25168386
• Disease models & mechanisms • 2022 • Variable phenotypes and penetrance between and within different zebrafish ciliary transition zone mutants PMID:36533556

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