Table 3.
Summary of CDC73 mutations associated with hyperparathyroidism‐jaw tumor
| Mutation a | Exon/intron | Codon b | Predicted effect c | Type d | Original designation | References |
|---|---|---|---|---|---|---|
| c.‐16_8del | Exon 1 | p.Met? | G | c.‐16:8del; p.Met1? | Bellido et al. (2016) | |
| c.3G > A | Exon 1 | 1 | p.Met? | G | 3G→A | Carpten et al. (2002)r |
| c.13_30del | Exon 1 | 5 | p.Leu5_Gln10del | Sp ,1 | 13_30delCTTAGCGTCCTGCGACAG | Moon et al. (2005) |
| c.18_46del | Exon 1 | 6 | p.Ser6ArgfsX50 | Gp | c.18_48del31 | Parfitt, Harris, Wright, and Kalamchi (2015) |
| c.14_17dup | Exon 1 | 7 | p.Val7X | Gp | c.14_17dupTTAG | Khadilkar et al. (2015)r , e |
| c.[24del;20T > C]q | Exon 1 | 7 | p.Val7AlafsX14 | G | nt20AGGACG→GGGAG | Aldred et al. (2006) |
| c.22del | Exon 1 | 8 | p.Leu8CysfsX13 | G | c.22delC | Carlson & Smith (2008) |
| c.25C > T | Exon 1 | 9 | p.Arg9X | G | 25C→T | Carpten et al. (2002)r |
| c.25C > T | Exon 1 | 9 | p.Arg9X | G | c.25 > T | Newey et al. (2010)f |
| c.25C > T | Exon 1 | 9 | p.Arg9X | ND | R9X | Schmidt, Bradrick, and Gabali (2009) |
| c.25C > T | Exon 1 | 9 | p.Arg9X | ND | p.Arg9Stop (R9X) | Mathews, Winchester, Alsaygh, Bartlett, and Luttrell (2016) |
| c.30del | Exon 1 | 10 | p.Gln10HisfsX11 | G | 30delG | Carpten et al. (2002)r |
| c.12_31dup | Exon 1 | 11 | p.Tyr11CysfsX17 | Gp | 41 bp duplication/insertion | Carpten et al. (2002)r |
| c.35_41del | Exon 1 | 12 | p.Asn12ArgfsX7 | G | 34delAACATCC | Carpten et al. (2002)r |
| c.40C > T | Exon 1 | 14 | p.Gln14X | G | c.40C > T | Khadilkar et al. (2015) |
| c.40del | Exon 1 | 14 | p.Gln14ArgfsX7 | Gp | 39delC | Carpten et al. (2002)r |
| c.40del | Exon 1 | 14 | p.Gln14ArgfsX7 | G | 39delC | Mizusawa et al. (2006) |
| c.40del | Exon 1 | 14 | p.Gln14ArgfsX7 | G | 39delC | Yamashita, Akiyama, Mizusawa, Yoshimoto, and Goto (2007) |
| c.70del | Exon 1 | 24 | p.Glu24LysfsX2 | Sp | c.70delG | Sriphrapradang et al. (2014) |
| c.76del | Exon 1 | 26 | p.Ile26SerfsX11 | G | c.76delA | Howell et al. (2003)g , h |
| c.76del | Exon 1 | 26 | p.Ile26SerfsX11 | Gp ,2 | c.76delA | Howell et al. (2003)g , h |
| c.76del | Exon 1 | 26 | p.Ile26SerfsX11 | Gp | c.76delA | Frank‐Raue et al. (2011) |
| c.85del | Exon 1 | 29 | p.Glu29SerfsX8 | Sp ,1 | 85delG | Moon et al. (2005) |
| c.85del | Exon 1 | 29 | p.Glu29SerfsX8 | G | 85del | Rekik et al. (2010) |
| c.85G > T | Exon 1 | 29 | p.Glu29X | G | c.93G > T exon 1 | Bricaire et al. (2013) |
| c.85G > T | Exon 1 | 29 | p.Glu29X | G | c.85G > T | Abdulla, O'Leary, Isorena, Diaz, and Yeh, (2013) |
| c.96G > A | Exon 1 | 32 | p.Trp32X | G | c.96G > A | Sarquis et al. (2008)h , i |
| c.96G > A | Exon 1 | 32 | p.Trp32X | NDp | c.96G > A | Kutcher et al. (2013) |
| c.131+1G > A | Intron 1 | splice [d]o | G | c.131+1G > A | Newey et al. (2010)f | |
| c.140_144del | Exon 2 | 47 | p.Lys47ArgfsX17 | G3 | c.136_144 del5 | Iacobone et al. (2009)h , j |
| c.165C > G | Exon 2 | 55 | p.Tyr55X | Gp | 165C‐G | Carpten et al. (2002)r |
| c.165C > A | Exon 2 | 55 | p.Tyr55X | NDp | c.165C > A | Veiguela, Isidro, Jorge, and Ruano (2010) |
| c.179T > A | Exon 2 | 60 | p.Ile60Asn | S3 | c.179T > A | Masi et al. (2014) |
| c.188T > C | Exon 2 | 63 | p.Leu63Pro | G | c.188T > C | Newey et al. (2010)f |
| c.188T > C | Exon 2 | 63 | p.Leu63Pro | G4 | c.188T > C | Iacobone et al. (2009)h , j |
| c.191T > C | Exon 2 | 64 | p.Leu64Pro | Gp | L64P | Hahn et al. (2010)g , h , k |
| c.205dup | Exon 2 | 69 | p.Leu69ProfsX13 | Gp | c.205dupC | Pichardo‐Lowden, Manni, Saunders and Baker (2011)l |
| c.226C > T | Exon 2 | 76 | p.Arg76X | G | c.226C > T | Newey et al. (2010)f |
| c.238‐1G > A | Intron 2 | splice [a]o | Gp ,1 | IVS2‐1G > A | Moon et al. (2005) | |
| c.284T > C | Exon 3 | 95 | p.Leu95Pro | G | L95P | Panicker, Zhang, Dagur, Gastinger and Simonds, (2010) |
| c.284T > C | Exon 3 | 95 | p.Leu95Pro | Sp ,5 | c.284T > C | Yu et al. (2015)h |
| c.306_307+13del | Exon 3 | 103 | p.Ser103AsnfsX5 | Gp | *306delGTgtgagtacttttt | Carpten et al. (2002)r |
| c.307+5G > T | Intron 3 | splice [vus] | G | c.307+5G > T | Frank‐Raue et al. (2011) | |
| c.356del | Exon 4 | 119 | p.Gln119ArgfsX14 | Gp ,5 | 356delA | Carpten et al. (2002)r , h |
| c.358C > T | Exon 4 | 120 | p.Arg120X | NDp | c.358C > T | Mele, Rolighed, Jespersen, Rejnmark and Christiansen (2016) |
| c.374_375dup | Exon 5 | 126 | p.Arg126AsnfsX8 | S4 | c.375_376insAA | Masi et al. (2008)h |
| c.406A > T | Exon 5 | 136 | p.Lys136X | G | 406A→T | Carpten et al. (2002)r |
| c.433_442delinsAGA | Exon 5 | 145 | p.Cys145ArgfsX55 | G | c.433_442delinsAGA | Iacobone et al. (2009) |
| c.424‐5T > C | Intron 5 | splice [vus] | G | c.424‐5T > C | Frank‐Raue et al. (2011) | |
| c.639del | Exon 7 | 213 | p.Phe213LeufsX6 | G | 636delT | Carpten et al. (2002)r |
| c.664C > T | Exon 7 | 222 | p.Arg222X | Gp | c.664C > T | Wang et al. (2012)r |
| c.668_669delinsG | Exon 7 | 223 | p.Asp223GlyfsX34 | Gp | 669delAT/insG | Bradley et al. (2005b)r , h |
| c.679_680insAG | Exon 7 | 227 | p.Arg227LysfsX31 | G | 679insAG | Bradley et al. (2005b)r , h |
| c.679_680insAG | Exon 7 | 227 | p.Arg227LysfsX31 | Gp | 679insAG | Carpten et al. (2002)r , h |
| c.686_689del | Exon 7 | 229 | p.Arg229AsnfsX27 | Sp ,2 | c.686delGAGT | Howell et al. (2003)g , h , m |
| c.687_688del | Exon 7 | 229 | p.Arg229SerfsX37 | G | c.679delAG | Howell et al. (2003)g , h |
| c.687_688del | Exon 7 | 229 | p.Arg229SerfsX37 | G | c.679delAG | Sarquis et al. (2008) |
| c.687_688del | Exon 7 | 229 | p.Arg229SerfsX37 | G | AGCACA^GAGAGagTATGGAGGACA | Teh et al. (2004)f , n |
| c.687_688del | Exon 7 | 229 | p.Arg229SerfsX37 | G | c.687_688del | Newey et al. (2010)f |
| c.700C > T | Exon 7 | 234 | p.Arg234X | G | 700C→T | Bradley et al. (2006) |
| c.700C > T | Exon 7 | 234 | p.Arg234X | Gp | R234X | Raue, Haag and Frank‐Raue (2007) |
| c.700C > T | Exon 7 | 234 | p.Arg234X | G | c.700C > T | Newey et al. (2010)f |
| c.745dup | Exon 8 | 249 | p.Ile249AsnfsX18 | G | c.745dupA | Newey et al. (2010)f |
| c.766_767del | Exon 8 | 256 | p.Val256LysfsX10 | G | 255delTG/256delGT | Cavaco et al. (2004) |
| c.1126_1127insTT | Exon 13 | 276 | p.Asn376IlefsX10 | G | 1126InsTT | Pimenta et al. (2006) |
| c.1135G > A | Exon 13 | 379 | p.Asp379Asn | G | 1135 G → A | Bradley et al. (2006) |
| c.1239del | Exon 14 | 413 | p.Gln413HisfsX15 | G | 1238delA | Carpten et al. (2002)r |
| c.1247del | Exon 14 | 416 | p.Gly416AlafsX12 | G | c.1247delG | Howell et al. (2009)f |
| c.1346del | Exon 15 | 449 | p.Gly449ValfsX30 | Gp | c.1346delG | Frank‐Raue et al. (2011) |
| c.1382del | Exon 15 | 461 | p.Leu461CysfsX18 | Gp | c.1379delT | Chiofalo et al. (2014) |
| c.1432_1433del | Exon 16 | 478 | p.Leu478GlufsX3 | G | c.1432_1433delCT | Frank‐Raue et al. (2011) |
| c.*12C > A | 3′‐UTR | Expression [vus] | G | c.*12C > A | Frank‐Raue et al. (2011) | |
| Gross deletion | G | c.307+?_513‐?del exons 4, 5, 6 | Kong et al. (2014) | |||
| Gross deletion | G | c.307+?_513‐?del exons 4, 5, 6 | Bricaire et al. (2013) | |||
| Gross deletion | Gp | 1q31,1–1q31,3 del | Bricaire et al. (2013)r | |||
| Gross deletion | G | Whole gene deletion | Cascon et al. (2011) | |||
| Gross deletion | Gp | Whole gene deletion | Bricaire et al. (2013)r |
Mutations are numbered in relation to the cell division cycle 73 (CDC73) cDNA reference sequence (GenBank accession number NM_024529.4) whereby nucleotide +1 corresponds to the A of the ATG‐translation initiation codon. All mutations were analyzed using the Leiden Open Variation Database (LOVD) Mutalyzer sequence variant nomenclature checker (https://www.lovd.nl/mutalyzer/) and annotated using the Human Genome Variation Society (HGVS) guidelines (https://www.hgvs.org/).
Codon numbering starts from initiation codon of CDC73 mRNA.
Predicted effect: splice, splice site mutation; [d] donor splice site; [a] acceptor splice site; [vus] variant of unknown significance; ? indicates unlikely translation of protein as initiator met is lost.
Mutation type: G, germline; S, somatic; ND, not defined. Equal superscript numbers represent germline and/or somatic mutations occurring in the same patient.
Criteria for diagnosis of PC were not reported, but the patient had persistent disease and clinical suspicion of thoracic metastasis.
Reported as HPT‐JT, but the authors did not provide details about the presence or absence of jaw tumors.
Additional clinical details about these kindreds are provided Bradley et al. (2005b).
Reported as HPT‐JT, but occurrence of jaw tumors, which may not always occur in HPT‐JT patients, was not detected in any family members.
Reported in other publication as a possible FIHP case, but the frequent recurrence, presence of APA and renal and uterine tumors favors the diagnosis of HPT‐JT (Silveira et al., 2008).
Initially reported as FIHP by Masi et al. (2008).
Initially reported as FIHP by Howell et al. (2003).
It is possible this is a case of HPT‐JT associated with PC since: the patient was diagnosed with three renal cysts, while “a maternal cousin had jaw pain and presumably bone destruction of the jaw, termed a ‘hole in the jaw’.” Furthermore, histological description of the proband's parathyroid gland was consistent with an APA (“…vascular and capsular invasion, but no definitive features of PC were identified”) and disease recurrence on the contra‐lateral side (again with diagnosis of APA) suggests a more malignant behavior.
Reported as a germline mutation in a later publication, but inconsistency between patients’ gender and age are observed (Sarquis et al., 2008).
Unclear if this kindred was included in the previous study of Howell et al. (2003).
For detailed information of the effect of CDC73 mutation on splicing please consult Hahn, McDonnell, and Marsh (2009).
Mutations identified in kindreds with case reports of PC.
Discordant codon/nucleotide change in the original report.
Criteria for diagnosis of PC not reported.
PC, parathyroid carcinoma; HPT‐JT, hyperparathyroidism‐jaw tumor; FIHP, familial isolated primary hyperparathyroidism; APA, atypical parathyroid adenoma.