Novel mutations associated with inherited human calcium-sensing receptor disorders: A clinical genetic study
Por:
Gaztambide, S, Ramirez, J, Gomez, M, Montalban, C, Ruiz, R, Socias, C, Boronat, M, Aparicio, C, Bilbao, I, Conde, S, Garcia-Cuartero, B, Jimenez, B, Rodriguez, P, Perez, E, Hidalgo-Barquero, E, Barrio, R, Gonzalez, C, Cordo, C, Cruz, J, Hernandez, J, Fernandez-Ramos, C, Marti, J, Clemente, M, Garcia, L, Rica, I, Martinez, R, Urrutia, I, de LaPiscina, I, Santos, F, Gil-Pena, H, Coto, E, Loredo, V, Ordonez, F, Rodriguez, J, Riera, E, Hernandez, O, Fuente, R, Claramunt, D, Nieto, V, Martin, F, Acosta, H, Trujillo, E, Yanes, M, Lanus, E, Castano, L, Madariaga, L, de Nanclares, G, Garcia-Castano, A, Aguirre, M, Herrero, M, Aguayo, A, Ariceta, G, Meseguer, A, Spanish Endocrinology Grp and Renal Tube Grp
Publicada:
1 ene 2019
Resumen:
Objective: Molecular diagnosis is a useful diagnostic tool in calcium metabolism disorders. The calcium-sensing receptor (CaSR) is known to play a central role in the regulation of extracellular calcium homeostasis. We performed clinical, biochemical and genetic characterization of sequence anomalies in this receptor in a cohort of 130 individuals from 82 families with suspected alterations in the CASR gene, one of the largest series described.
Methods: The CASR gene was screened for mutations by polymerase chain reaction followed by direct Sanger sequencing.
Results: Presumed CaSR-inactivating mutations were found in 65 patients from 26 families. These patients had hypercalcemia (median: 11.3 mg/dL) but normal or abnormally high parathyroid hormone (PTH) levels (median: 52 pg/ mL). On the other hand, presumed CaSR-activating mutations were detected in 17 patients from eight families. These patients had a median serum calcium level of 7.4 mg/dL and hypoparathyroidism (median: PTH 13 pg/mL). Further, common polymorphisms previously associated with high blood ionized calcium levels were found in 27 patients (median calcium: 10.6 mg/dL; median PTH: 65 pg/mL) with no other alterations in CASR. Overall, we found 30 different mutations, of which, 14 have not been previously reported (p.Ala26Ser, p.Cys60Arg, plys119lle, p.Leu123Met, p.Glu133Val, p.Gly222Glu, p.Phe351lle, p.Cys542Tyr, p.Cys546Gly, p.Cys677Tyr, p.lle816Val, p.Ala887Asp, p.Glu934*, p.Pro935_Gln945dup).
Conclusions: Patients with CASR mutations may not fit the classic clinical pictures of hypercalcemia with hypocalciuria or hypocalcemia with hypercalciuria. Molecular studies are important for confirming the diagnosis and distinguishing it from other entities. Our genetic analysis confirmed CaSR disorders in 82 patients in the study cohort.
Filiaciones:
Gaztambide, S:
Biocruces Bizkaia Hlth Res Inst, CIBERER, CIBERDEM, Baracaldo, Spain
Univ Basque Country, Hosp Univ Cruces, Baracaldo, Spain
Ramirez, J:
Hosp Univ Principe Asturias, Madrid, Spain
Gomez, M:
Hosp Univ Principe Asturias, Madrid, Spain
Montalban, C:
Hosp Sierrallana, Torrelavega, Spain
Ruiz, R:
Complejo Hosp Univ, Albacete, Spain
Socias, C:
Hosp Bidasoa, Hondarribia, Spain
Boronat, M:
Complejo Hosp Univ Insular Materno Infant, Las Palmas Gran Canaria, Spain
Aparicio, C:
Hosp Univ, Getafe, Spain
Bilbao, I:
Hosp Univ, Donostia San Sebastian, Spain
Conde, S:
Hosp Barbastro, Huesca, Spain
Garcia-Cuartero, B:
Hosp Univ Severo Ochoa, Leganes, Spain
Jimenez, B:
Hosp Juan Ramon Jimenez, Huelva, Spain
Rodriguez, P:
Hosp Juan Ramon Jimenez, Huelva, Spain
Perez, E:
Hosp Univ Virgen Macarena, Seville, Spain
Hidalgo-Barquero, E:
Hosp Materno Infantil, Badajoz, Spain
Barrio, R:
Hosp Univ Ramon Y Cajal, Madrid, Spain
Gonzalez, C:
Hosp Rafael Mendez, Lorca, Spain
Cordo, C:
Complejo Hosp Univ, Vigo, Spain
Cruz, J:
Hosp Univ 12 Octubre, Madrid, Spain
Hernandez, J:
Hosp Galdakao, Galdakao, Spain
Fernandez-Ramos, C:
Hosp Univ Basurto, Bilbao, Spain
Marti, J:
Hosp Zumarraga, Zumarraga, Spain
Clemente, M:
Hosp Univ Vall dHebron, Barcelona, Spain
:
Hosp Sagunto, Sagunto, Spain
Rica, I:
Hosp Univ Cruces, Biocruces Bizkaia Hlth Res Inst, Baracaldo, Spain
Martinez, R:
Hosp Univ Cruces, Biocruces Bizkaia Hlth Res Inst, Baracaldo, Spain
Urrutia, I:
Hosp Univ Cruces, Biocruces Bizkaia Hlth Res Inst, Baracaldo, Spain
de LaPiscina, I:
Hosp Univ Cruces, Biocruces Bizkaia Hlth Res Inst, Baracaldo, Spain
Santos, F:
Hosp Univ Cent Asturias, Oviedo, Spain
Gil-Pena, H:
Hosp Univ Cent Asturias, Oviedo, Spain
Coto, E:
Hosp Univ Cent Asturias, Oviedo, Spain
Loredo, V:
Hosp Univ Cent Asturias, Oviedo, Spain
Ordonez, F:
Hosp Univ Cent Asturias, Oviedo, Spain
Rodriguez, J:
Hosp Univ Cent Asturias, Oviedo, Spain
Riera, E:
Hosp Univ Cent Asturias, Oviedo, Spain
Hernandez, O:
Hosp Univ Cent Asturias, Oviedo, Spain
Fuente, R:
Hosp Univ Cent Asturias, Oviedo, Spain
Claramunt, D:
Hosp Univ Cent Asturias, Oviedo, Spain
Nieto, V:
Hosp Univ Nuestra Senora Candelaria, Tenerife, Spain
Martin, F:
Hosp Univ Nuestra Senora Candelaria, Tenerife, Spain
Acosta, H:
Hosp Univ Nuestra Senora Candelaria, Tenerife, Spain
Trujillo, E:
Hosp Univ Nuestra Senora Candelaria, Tenerife, Spain
Yanes, M:
Hosp Univ Nuestra Senora Candelaria, Tenerife, Spain
Lanus, E:
Hosp Univ Nuestra Senora Candelaria, Tenerife, Spain
Castano, L:
Biocruces Bizkaia Hlth Res Inst, CIBERER, CIBERDEM, Baracaldo, Spain
Univ Basque Country, Hosp Univ Cruces, Baracaldo, Spain
Hosp Univ Cruces, Baracaldo, Spain
Madariaga, L:
Biocruces Bizkaia Hlth Res Inst, CIBERER, CIBERDEM, Baracaldo, Spain
Univ Basque Country, Hosp Univ Cruces, Baracaldo, Spain
Hosp Univ Cruces, Baracaldo, Spain
de Nanclares, G:
Biocruces Bizkaia Hlth Res Inst, CIBERER, CIBERDEM, Baracaldo, Spain
Univ Basque Country, Hosp Univ Cruces, Baracaldo, Spain
Hosp Univ Cruces, Baracaldo, Spain
Garcia-Castano, A:
Biocruces Bizkaia Hlth Res Inst, CIBERER, CIBERDEM, Baracaldo, Spain
Hosp Univ Cruces, Baracaldo, Spain
Aguirre, M:
Hosp Univ Cruces, Baracaldo, Spain
Herrero, M:
Hosp Univ Cruces, Baracaldo, Spain
Aguayo, A:
Hosp Univ Cruces, Baracaldo, Spain
Ariceta, G:
Autonomous Univ Barcelona, Hosp Univ Materno Infantil Vall dHebron, Barcelona, Spain
Hosp Univ Materno Infantil Vall DHebron, Barcelona, Spain
Meseguer, A:
Hosp Univ Materno Infantil Vall DHebron, Barcelona, Spain
Open Access
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