Biallelic Variants in MIMS1 Produce a Form of Spondyloepimetaphyseal Dysplasia With Tracheal Stenosis and Ectodermal Dysplasia (SEMDTSED).

Biallelic loss-of-function MIMS1 (formerly FAM210A) variants clustering in the DUF1279 domain

Via GeneMatcher, the authors identify five individuals from four unrelated families with a skeletal dysplasia and biallelic deleterious MIMS1 (formerly FAM210A) variants. Common features combine chondrodysplasia with short stature, tracheal stenosis, conical teeth or early decay, and sparse hair suggesting ectodermal dysplasia. Radiographic features (platyspondyly, epiphyseal dysplasia, short phalanges) match a spondyloepimetaphyseal dysplasia. Missense variants cluster in the conserved DUF1279 domain, with one family carrying compound heterozygous nonsense variants, supporting a loss-of-function mechanism; the name SEMDTSED, MIMS1-related is proposed.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A new gene-disease relationship well documented clinically and radiologically, driven by GeneMatcher data sharing. Evidence remains chiefly genetic and correlative (no dedicated functional assay), warranting replication. As the target is captured by WES, the challenge will be recognizing this presentation when interpreting biallelic MIMS1 variants.

Analysis by Dr Thibaut Benquey