In a 38-year-old woman with acromesomelic dysplasia (AMD3; 609441), who was born to first-cousin parents originating from Morocco, Stange et al. (2015) identified a homozygous c.91C-T transition (c.91C-T, NM_001256794.1) in the BMPR1B gene, resulting in an arg31-to-cys (R31C) substitution. Three of her sibs were reportedly affected, but DNA was not available for testing from any of her family members. The mutation was not identified in exome sequences from 30 Moroccan patients with unrelated disorders, and no R31C homozygotes or heterozygotes were present in the 5,718 exomes in the Institut Imagine (Paris) in-house database, which is enriched for exomes of Maghrebian individuals and contains a conservatively estimated 33 Moroccan exomes. By confocal microscopy, Stange et al. (2015) showed that the mutant R31C receptor was translocated at the cell surface. A luciferase reporter gene assay revealed that the R31C mutant could be stimulated by GDF5, but its signal had diminished biologic activity compared to wildtype BMPR1B. Stange et al. (2015) diagnosed the patient with Du Pan acromesomelic dysplasia (AMD2B; 228900), which is caused by mutation in the GDF5 gene (601146).
