Table 1.
Summary of published and unpublished MRAP mutations. The majority of mutations are predicted to result in absent or significantly truncated protein forms and hence complete loss of ACTH response. In comparison, c.76T>C (p.V26A) and c.175T>G (p.Y59D) have been shown to have impaired but not absent function. p.0? represents the recommended annotation when the effect on the protein is unknown as in the case of c.3G>A that affect the initiation site and the splice mutations the lead to skipping of exon 3.
| Mutationa | Mutation type | Functional effect | Clinical presentation | References |
|---|---|---|---|---|
| c.3G>A (p.0? or p.M1?) | MS | Unknown (? no protein produced) | Classical early onset | (2, 7, 25, 26) |
| c.17-23delACGCCTC (p.N6MfsX24) | NS | Shortened protein if translated | Classical early onset | (8) |
| c.33C>A (p.Y11X) | NS | Shortened protein if translated | Classical early onset | (1) |
| c.76T>C (p.V26A) | MS | Full-length protein with amino acid change – impaired cAMP generation | Late presentation | (4) |
| c.106+1G>T (p.0?) | SS | Skipping of exon 3 (no protein or lack transmembrane domain) | Classical early onset | (2, 7) |
| c.106+1G>A (p.0?) | SS | Skipping of exon 3 (no protein or lack transmembrane domain) | Classical early onset | (2, 7) |
| c.106+1G>C (p.0?) | SS | Skipping of exon 3 (no protein or lack transmembrane domain) | Classical early onset | (2, 7) |
| c.106+1delG (p.0?) | SS | Skipping of exon 3 (no protein or lack transmembrane domain) | Classical early onset | (2, 7, 27) |
| c.106+2insT (p.0?) | SS | Skipping of exon 3 (no protein or lack transmembrane domain) | Classical early onset | (2, 7) |
| c.106+2_3dupTA (p.0?)* | SS | Skipping of exon 3 (no protein or lack transmembrane domain) | Classical early onset | This study |
| c.128delG (p.V44X) | NS | Shortened protein if translated | Classical early onset | (7, 16) |
| c.175T>G (p.Y59D) | MS | Full-length protein with amino acid change – impaired cAMP generation | Late presentation | (4) |
MS, missense mutation; NS, nonsense mutation; SS, splice-site mutation; c., coding DNA; p., protein.
a
Mutations described according to recommended nomenclature (11). Novel mutation indicated by *.