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TMEM107 – Ciliopathy

TMEM107 variants have been implicated in an autosomal recessive ciliopathy. A single proband homozygous for c.295TTC (p.Phe100del) presented with polydactyly and reduced ciliated cell numbers, meeting diagnostic criteria for a ciliopathy (PMID:26518474). No segregation data or additional affected relatives have been reported.

Functional studies in patient-derived cells and Tmem107 mutant mice demonstrate mislocalization of key ciliary proteins and a decreased number of ciliated cells, mirroring the human phenotype and confirming a conserved role for TMEM107 in regulating ciliary protein composition (PMID:26518474). Collectively, the current evidence supports a limited clinical validity for TMEM107 in ciliopathy pending further case reports and segregation analyses. Key take-home: TMEM107 should be included in genetic testing panels for unexplained ciliopathies presenting with polydactyly.

References

  • Human mutation • 2016 • TMEM107 Is a Critical Regulator of Ciliary Protein Composition and Is Mutated in Orofaciodigital Syndrome. PMID:26518474

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single proband with homozygous c.295TTC (p.Phe100del) variant in TMEM107, no segregation data; moderate functional concordance ([PMID:26518474]).

Genetic Evidence

Limited

Single case report of a homozygous in-frame deletion in TMEM107.

Functional Evidence

Moderate

Patient-derived and mouse model studies show disrupted ciliary protein localization and reduced ciliated cell numbers consistent with the human phenotype ([PMID:26518474]).