Table 2.
Genetic and clinical characteristics of patients displaying germline variants in any of the genes included in the panel.
| ID | Age | Sex | Gene | Variant | Variant type | ACMG | ACMG classification |
Previously reported (gnomAD / Pubmed) | Ca Pre | Ca Post |
PTH Pre |
PTH Post |
Cr | CCCR | Inclusion criteria* | Pathology | Gland weight (gr) | Identified carriers |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 18 | 47 | M | CDKN1B | c.280_281delinsG, p.(Pro94Alafs*25) | Frameshift | LP | PVS1 (very strong), PM2 (supporting) | No / No | 3.39 | 2.20 | 55.24 | 6.89 | 1.07 | NA | 3 | APA | 15.7 | Mother (colon neoplasm) |
| 29 | 34 | M | CDKN1B | c.169C>T, p.(Gln57*) | Nonsense | P | PVS1 (very strong), PM2 (moderate) | No / No | 3.37 | 2.15 | 379.1 | 6.25 | 2.20 | 0.010 | 9 (1, 3, 5, 8) | MGD: 3 parathyroid hyperplasia glands and 1 APA | 1.7 | None |
| 27 | 28 | F | CDKN2C | c.319T>G, p.(Leu107Val) | Missense | VUS | PM2 (moderate) | 0.0036%/ No | 2.84 | 1.97 | 9.43 | 4.55 | 0.90 | 0.030 | 9 (1, 4) | MGD: 1 cystic adenoma and 1 parathyroid adenoma | 0.1 | Mother (PHPT) |
| 15 | 77 | M | CASR | c.1172T>G, p. (Phe391Cys) |
Missense | LP | PM2 (moderate), PP3 (supporting) PP2 |
No / No | 4.12 | 1.68 | 212.93 | 3.39 | 1.07 | 0.005 | 9 (3, 4, 5) | MGD: 1 APA (with cystic cells) and 1 hyperplasia gland | 1.33 | Son (asymptomatic PHPT) |
| 21 | 49 | M | CASR | c.413C>T, p. (Thr138Met) |
Missense | P | PM1 (moderate), PP2 (supporting), PM2 (moderate), PP3 (supporting), PP5 (strong) | No / Yes | 3.12 | - | 15.37 | - | 0.80 | 0.004 | 7 | - | NA | Daughter with symptomatic PHPT (not genetic test performed) |
| 24 | 64 | F | CASR | c.2393C>T, p. (Pro798Leu) |
Missense | LP | PM1 (moderate), PP2 (supporting), PM2 (moderate), PP3 (supporting), PP5 (strong) | No / Yes | 2.80 | 2.34 | 13.78 | 7.74 | 0.46 | 0.013 | 9 (5, 6) | MGD: 3 lipohyperplasia glands | 0.28 | 2 sons and 1 daughter with asymptomatic PHPT |
| 31 | 75 | F | CASR | c.175G>A, p. (Glu59Lys) |
Missense | VUS | PM1 (supporting), PM2 (supporting), BP4 (moderate) | No / No | 2.45 | 2.33 | 12.08 | 8.69 | 1.02 | 0.011 | 5 | MGD: 2 hyperplasia glands | 0.08 | 2 sisters and 1 brother with mild PHPT (normal calcium) |
| 4 | 41 | M | TRPV6 | c.1937G>A, p. (Arg646Gln) |
Missense | VUS | PM2 (moderate) | 0,0032% | 3.30 | 2.43 | 15.90 | 3.71 | 0.91 | 0.011 | 1 | Parathyroid adenoma | 0.4 | NA |
| 30 | 35 | F | TRPV6 | c.787G>A, p. (Asp263Asn) |
Missense | VUS | PM2 (moderate | 0,0415% | 2.75 | - | 15.58 | - | 0.62 | 0.010 | 1 | - | - | NA |
ID: identification number of each case; RV: reference value; Age: age at diagnosis of primary hyperparathyroidism; F: female; M: male; ACMG: variant classification according to ACMG guidelines; LP: likely pathogenic; P: pathogenic; VUS: variant of uncertain significance; Ca-Pre (mmol/L): corrected serum calcium pre-surgery (RV 2.1-2.55); Ca-Post (mmol/L): corrected serum calcium post-surgery; PTHPre (pmol/L): serum parathyroid hormone pre-surgery (RV 1.06-6.89); PTHPost: serum parathyroid hormone post-surgery; Cr: serum creatinine at diagnosis of primary hyperparathyroidism; CCCR: Calcium creatinine clearance ratio; APA: atypical parathyroid adenoma; MGD: multigland disease; Carriers: family members who carried the same variant and their clinical characteristics; PHPT: primary hyperparathyroidism; NA: not available; * Inclusion criteria (indication for genetic testing): 1: age ≤45 years old; 2: parathyroid carcinoma; 3: atypical parathyroid adenoma; 4: cystic parathyroid adenoma; 5: multiglandular disease; 6: recurrent hyperparathyroidism 3 months after surgery; 7: family history of primary hyperparathyroidism; 8: associated tumour suggestive of familial syndrome; 9: ≥2 inclusion criteria.