SNAI2 – Waardenburg syndrome type 2

The association between SNAI2 and Waardenburg syndrome type 2 has been investigated through targeted genetic screening. Two independent cohorts comprising three pedigrees (0/3 families; no pathogenic SNAI2 variants detected) (PMID:26781036) and 25 unrelated probands (0/25; no SNAI2 variants found) (PMID:29407415) yielded negative results for coding or splicing mutations in SNAI2. No segregation data or recurrent alleles have been reported.

To date, there are no published functional or experimental studies implicating SNAI2 in melanocyte development, neural crest migration, or pigmentary and auditory phenotypes characteristic of Waardenburg syndrome type 2. Established disease genes in WS2 include MITF, PAX3, SOX10 and EDNRB, whereas SNAI2 has not demonstrated pathogenicity in available assays.

The consistent absence of SNAI2 variants in WS2 patients across multiple cohorts and the lack of supporting functional data argue against a primary role for SNAI2 in the etiology of Waardenburg syndrome type 2. Continued exploration of noncoding regions or modifier effects may be warranted but current evidence remains limited.

Key take-home: Routine diagnostic screening of SNAI2 is not recommended in Waardenburg syndrome type 2 molecular panels.

References

• Molecular medicine reports • 2016 • Clinical and genetic investigation of families with type II Waardenburg syndrome. PMID:26781036
• European journal of medical genetics • 2018 • Waardenburg syndrome: Novel mutations in a large Brazilian sample. PMID:29407415

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