Skeletal dysplasiaGene: SMAD6
Comment on list classification: New gene added by Tracy Lester (Genetics laboratory, Oxford UK). This gene is associated with a phenotype in OMIM and Gene2Phenotype.
Based on the available evidence it is recommended that this gene be given Green status at the next review.
Created: 1 Feb 2021, 11:33 a.m. | Last Modified: 1 Feb 2021, 11:33 a.m.
Panel Version: 2.81
SMAD6 is frequently mutated in non-syndromic radioulnar synostosis.Using exome seq the authors found 16 LOF and 6 rare missense variants in sporadic cases, which was a highly significant association. The findings were replicated in a different cohort. Four cases had de novo variants and others were inherited in a dominant fashion.
SMAD6 LOF variants have also been shown to be enriched in mid-line craniosynostosis and in certain cardiac disorders. It isn't yet clear if a variant can cause different phenotypes in the same family or combinations of these phenotypes in the same individual. Genotype-phenotype correlation is not understood.
This gene is currently tested diagnostically in cases of mid-line craniosynostosis and is green on panel R100.
Sources: NHS GMS
Created: 30 Jan 2021, 10:03 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: smad6 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: SMAD6.
gene: SMAD6 was added gene: SMAD6 was added to Skeletal dysplasia. Sources: NHS GMS Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMAD6 were set to 31138930 Phenotypes for gene: SMAD6 were set to Radioulnar synostosis Penetrance for gene: SMAD6 were set to Incomplete Review for gene: SMAD6 was set to GREEN