Table 2.
Summary of clinical information from families affected by germline DICER1 Platform missense variants. Clinical information from reports of germline pathogenic missense variants in the platform domain of DICER1 with additional information provided in this study. Tumors that have been resected and pathology has been confirmed are indicated in bold. Question mark uncertainty of the age of diagnosis. cERMS: cervical embryonal rhabdomyosarcoma; Dx: diagnosis; MNG: multinodular goiter; N/A: not available
| Germline variant (original publication) | Individual | Sex | DICER1-associated disease status (age in years at dx) | Mutation status | Second hit |
|---|---|---|---|---|---|
| DICER1 c.2407G>A, p.G803R (Palculict et al., 2016, with additional clinical information provided in this study) | III-2 | F | Thyroidectomy (18) | Present | Not known |
| IV-2 | F | Unaffected | Absent | Not applicable | |
| IV-4 | F | Unaffected | Absent | Not applicable | |
| IV-5 | M | Unaffected | Present | Not applicable | |
| IV-7 | F | Wilms tumor (8) | Present | Wilms tumor: Loss of heterozygosity (LOH) (patient tested unspecified) | |
| IV-8 | M | Wilms tumor (4) | Present | ||
| V-5 | M | Wilms tumor (4) | Present | ||
| V-6 | F | Unaffected | Absent | ||
| V-8 | F | Wilms tumor (2) Thyroid nodular hyperplasia (16) | Present | In this study: MNG: c.5428G>C, p.D1810H | |
| VI-1 | M | Unaffected | Absent | Not applicable | |
| DICER1 c.2414T>C, p.L805P (Diets et al., 2018) | I-1 | M | Unaffected | Present | Not applicable |
| I-2 | F | Unaffected | Absent | Not applicable | |
| II-1 | F | cERMS (4) | Present | cERMS: c.5439G>T, p.E1813D | |
| DICER1 c.2516C>T, p.S839F (Rio Frio et al., 2011) | See table 1D from Rio Frio et al., 2011, for information regarding the 20 cases of MNG diagnosed in persons carrying with the p.S839F variant | MNG: c.5428G>T, p.D1810Y and c.5439G>T, p.E1813D (de Kock et al., 2016) | |||
| DICER1 c.2642T>C, p.L881P (Van Engelen et al., 2017 and second hit provided in this study) | I-1 | N/A | MNG (?) | N/A | Not known |
| II-1 | N/A | Goiter (?) | N/A | Not known | |
| II-2 | M | Unaffected | Present | Not applicable | |
| III-1 | F | Cystic nephroma (1.1) Pineal cyst (3.8) | Present | In this study: cystic nephroma: c.5125G>A, p.D1709N | |