Monogenic hearing loss

Gene: DSPP

Red List (low evidence)

Comment on list classification: There is limited and conflicting evidence regarding the association between DSPP variants and dominant hearing loss. There are 3 Chinese families reported with DSPP missense variants and hearing loss, including one pedigree with a common likely benign variant. The other two families had both dentinogenesis imperfecta and hearing loss, and harboured the same DSPP variant detected by linkage analysis/targeted DSPP seq - another gene likely responsible for hearing loss. In addition, numerous other cases with 59+ different DSPP variants have been reported in literature with isolated dentinogenesis imperfecta.

Created: 26 May 2026, 12:18 p.m. | Last Modified: 26 May 2026, 12:18 p.m.

Panel Version: 6.15

PMID: 11175790 Xiao et al., 2001
2 Chinese families with sensorineural hearing loss and dentinogenesis imperfecta (DI), both het for DSPP variant c.49C>A (p.Pro17Thr). Method: linkage analysis, followed by DSPP sequencing.

PMID: 17686168
Chinese family with DI and the same DSPP residue mutated as in PMID: 11175790 (c.49C>T, p.Pro17Ser), and no hearing loss.

PMID: 29741433 Li et al., 2018
Chinese proband with Familial nonsyndromic hearing loss (NSHL) with incomplete partition type II, harboured DSPP c.3085A>G, p.Asn1029Asp and c.3087C>T, p.Asn1029= variants in cis. Method: WGS of proband and 7 family members. 3 affected individuals: father and his two male sons (twins), all with the same DSPP allele.
Both DSPP variants have high gnomAD frequencies in East Asian population (0.01039 and 0.009011), with homozygous individuals also reported; p.Asn1029Asp is Likely Benign in ClinVar - unlikely to be causal.

PMID: 33229591 Boucher et al., 2020
Age-related hearing loss cohort. Patient 6708 - harboured a c.776C > T; p.(Ser259Phe) variant in DSPP.

Hearing loss has not been mentioned as a feature in numerous other cases with DSPP variants and DI (59 variants reported in literature according to PMID: 39806231 Gilani, Saikia, and Anthonappa, 2025).

Created: 26 May 2026, 10:40 a.m. | Last Modified: 26 May 2026, 11:56 a.m.

Panel Version: 6.13

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Deafness, autosomal dominant 39, with dentinogenesis, OMIM:605594; Dentin dysplasia, type II, OMIM:125420; Dentinogenesis imperfecta, Shields type II, OMIM:125490; Dentinogenesis imperfecta, Shields type III, OMIM:125500

Publications

• 11175790
• 17686168
• 29741433
• 33229591
• 39806231

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
#125420:Dentin dysplasia, type II[Amber, translucent coloration (primary teeth)Obliteration of pulp chambers following eruption (primary teeth)Normal-shaped roots (primary teeth)Normal coloration (secondary teeth)Thistle-shaped pulp chambers (secondary teeth)Multiple pulp stones (secondary teeth)Normal-shaped roots (secondary teeth)]; #125490:Dentinogenesis imperfecta, Shields type II[Dentinogenesis imperfectaBrown-blue or opalescent brown teethBulbous shaped crownNarrow rootsRoot canals are small or obliteratedAbsent pulp chambersSevere attritionPrimary and secondary teeth affected]; #125500:Dentinogenesis imperfecta, Shields type III[Anterior openbite; Primary and secondary teeth affectedAmber-opalescent colored teeth (primary and secondary)Marked attrition (primary and secondary)Enamel pitting (secondary)Normal-to-enlarged pulp chamber (primary)Obliterated pulp chamber (secondary)Periapical radiolucenciesPulp exposuresIncisal notchingShell teethBulbous tooth crowns]; #605594:Deafness, autosomal dominant 39, with dentinogenesis[Progressive high-frequency hearing loss (onset 20-30 years)Tinnitus; Dentinogenesis imperfecta]

Publications

• PMID:10706475
• 11116156
• 11175770
• 11175779
• 11175790
• 12354781
• 12721295
• 14758537
• 15592686
• 15954904
• 17210923
• 18456718
• 22392858
• 22582013
• 2433419
• 2462619
• 7573043
• 8995371
• 9533027

Comment on list classification: Good evidence from expert reviewer and OMIM

Created: 31 Jan 2016, 7:41 p.m.