SOX10 – deaf blind hypopigmentation syndrome, Yemenite type

Yemenite deaf-blind hypopigmentation syndrome is an autosomal dominant neurocristopathy characterized by patchy hypopigmentation, microcornea, coloboma and severe hearing impairment. Affected individuals in two independent families (two siblings and one sporadic case) harbor a heterozygous SOX10 missense variant c.404G>C (p.Ser135Thr) that abolishes DNA binding of the HMG domain, establishing a primary genetic etiology for the mild form of this syndrome (PMID:10441344). No additional familial segregation has been observed.

Functional assays demonstrate that the S135T mutant protein fails to activate both MITF and EDNRB promoters, yet retains partial synergy with Sp1, indicating a dominant-negative effect on SOX10 transcriptional activity and supporting a haploinsufficiency mechanism (PMID:16921166). These data provide moderate experimental support for pathogenicity. Together, limited genetic evidence and concordant functional data define the clinical validity of SOX10 in Yemenite deaf-blind hypopigmentation syndrome as Limited. SOX10 molecular testing should be considered in patients with this phenotype.

References

• Human molecular genetics • 1999 • A molecular analysis of the yemenite deaf-blind hypopigmentation syndrome: SOX10 dysfunction causes different neurocristopathies. PMID:10441344
• Journal of biochemistry • 2006 • Functional difference of the SOX10 mutant proteins responsible for the phenotypic variability in auditory-pigmentary disorders. PMID:16921166

Evidence Based Scoring (AI generated)