Amelogenesis imperfecta

Gene: SMOC2

Red List (low evidence)

Comment on list classification: After review by the Genomics England Clinical Team, it was decided that Dentin Dysplasia is not in scope of the Amelogenesis imperfecta (AI) panel, as it is readily distinguishable from AI by dental specialists. Individuals reported with SMOC2 variants do not present with osteogenesis imperfecta, either. However, oligodontia and tooth shape abnormalities associated with this gene can be investigated through the R163 Ectodermal dysplasia panel. Hence, the rating should remain Red for Amelogenesis imperfecta, but SMOC2 will be proposed for promotion on the Ectodermal dysplasia panel.

Created: 5 Oct 2026, 3:22 p.m. | Last Modified: 5 Oct 2026, 3:23 p.m.

Panel Version: 4.39

PMID: 22152679 Bloch-Zupan et al., 2011
Report of a severe developmental dental defect that results in a dentin dysplasia phenotype with major microdontia, oligodontia, and shape abnormalities in a highly consanguineous family. 2 affected children were found to carry a homozygous mutation in SMOC2: c.84+1G>T. Unaffected sibs were heterozygous for the variant. Method: Homozygosity mapping, WES, direct sequencing - SMOC2 was poorly covered on exome.
Knockdown of smoc2 in zebrafish showed pharyngeal teeth that had abnormalities reminiscent of the human phenotype.

PMID: 23317772 Alfawaz et al., 2013
Consanguineous Pakistani family with oligodontia and microdontia. WES detected a homozygous SMOC2 c.681T>A (p.C227X) mutation in 2 affected individuals.

PMID: 32908163 Morkmued et al., 2020
Same group as PMID: 22152679 Bloch-Zupan et al.
Follow up of a 9yo female patient from the 2011 study. Radiographs showed severe oligodontia, microdontia, tooth root deficiencies, alveolar bone hypoplasia, and some skeletal dysplasia features: hyperlordotic curved spinal column, platyspondyly, wider iliac wings.
Mouse model: homozygous smoc2 mutant mice had tooth number anomalies, reduced tooth size, altered enamel prism patterning, and spontaneous age-induced periodontal bone and root loss, supportive of disease association.

SMOC2 is associated with AR Dentin dysplasia, type IA, OMIM:125400 in OMIM (accessed 5th Jun 2026).
Sources: Literature

Created: 5 Jun 2026, 4:16 p.m. | Last Modified: 5 Jun 2026, 4:28 p.m.

Panel Version: 4.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dentin dysplasia, type IA, OMIM:125400; atypical dentin dysplasia due to SMOC2 deficiency, MONDO:0017819; dentin dysplasia type 1 with microdontia and shape anomalies

Publications

• 22152679
• 23317772
• 32908163