SLC30A7 – Joubert Syndrome

Recent evidence has implicated SLC30A7 in Joubert syndrome based on de novo heterozygous variants observed in two unrelated probands exhibiting classic features including the molar tooth sign, ataxia, oculomotor apraxia, macrocephaly, neurodevelopmental delay, precocious puberty, as well as postaxial polydactyly and accessory oral frenulum (PMID:35751429). In one case, a missense variant, c.407 > C (p.Val136Ala), was identified, while a second case harbored a distinct deletion-insertion variant; both variants affect residues that are highly conserved and were absent from established Joubert syndrome gene panels.

Complementary functional investigations provide further support for the candidate role of SLC30A7. Studies using bimolecular fluorescence complementation confirmed that SLC30A7 can form homodimers and interact with proteins involved in ciliary function, such as TCTN3, thereby offering mechanistic plausibility that disruption of zinc transporter activity may impair ciliary signaling—a hallmark in Joubert syndrome pathology (PMID:24451381). Although the genetic evidence remains limited to two probands, the integration of supportive functional data encourages further consideration of SLC30A7 in diagnostic evaluations for JS.

References

• American journal of medical genetics. Part A • 2022 • De novo heterozygous variants in SLC30A7 are a candidate cause for Joubert syndrome PMID:35751429
• The Journal of biological chemistry • 2014 • In situ dimerization of multiple wild type and mutant zinc transporters in live cells using bimolecular fluorescence complementation PMID:24451381

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