Two further patients with the 1q24 deletion syndrome expand the phenotype: A possible role for the miR199–214 cluster in the skeletal features of the condition

Abstract

Submicroscopic deletions within chromosome 1q24q25 are associated with a syndromic phenotype of short stature, brachydactyly, learning difficulties, and facial dysmorphism. The critical region for the deletion phenotype has previously been narrowed to a 1.9 Mb segment containing 13 genes. We describe two further patients with 1q24 microdeletions and the skeletal phenotype, the first of whom has normal intellect, whereas the second has only mild learning impairment. The deletion in the first patient is very small and further narrows the critical interval for the striking skeletal aspects of this condition to a region containing only Dynamin 3 (DNM3) and two microRNAs that are harbored within intron 14 of this gene: miR199 and miR214. Mouse studies raise the possibility that these microRNAs may be implicated in the short stature and skeletal abnormalities of this microdeletion condition. The deletion in the second patient spans the previously reported critical region and indicates that the cognitive impairment may not always be as severe as previous reports suggest.

1q24 deletion syndrome. Two cases and new insights into genotype‐phenotype correlations

“…With regards to the skeletal phenotype, our cases provide further evidence supporting the significance of DNM3 and/or miR199–214 in the skeletal features, as suggested by Ashraf et al (). There has been no published evidence to suggest a role for DMN3 in skeletal development.…”

“…However, mouse studies support a potential role for miRNA199–214 in skeletal development (Watanabe et al, ). Functional studies have also indicated involvement of both miR199 and miR214 in bone formation (Ashraf et al, ). There is emerging evidence to suggest that miR214 is involved in regulating the Wnt/B catenin signaling pathway in the development of human osteosarcoma.…”

“…In addition, the patient responded to treatment with growth hormone (Lam & Morris, ). None of the previously reported patients has shown a significant response to growth hormone (Ashraf et al, ; Burkardt et al, )…”

“…Ashraf et al () reported two further patients with typical features but smaller deletions, one of which contained only three genes. This further narrowed the critical region for the skeletal features.…”

MicroRNAs in orthopaedic research: Disease associations, potential therapeutic applications, and perspectives

“…[59][60][61][62][63][64] Recently, Ashraf et al reported two additional patients with microdeletions in 1q24q25 that display similar skeletal abnormalities as reported previously (i.e., short stature, brachydactyly, and facial dysmorphism). 65 The deletion mutation in one of these patients narrowed down the critical region causing these skeletal defects to that encoding dynamin-3 (DNM3) and two miRNAs located within intron 14 of this gene (miR-199a and miR-214). Interestingly, a study by Watanabe et al showed skeletal defects in mice devoid of the long non-coding RNA, Dnm3os, an antisense transcript in intron 14 of Dnm3 that harbors both miR-199a and miR-214.…”