Comprehensive Genetic Testing of CYP21A2: A Retrospective Analysis in Patients with Suspected Congenital Adrenal Hyperplasia
Por:
Nan, MN, Roig, R, Martinez, S, Rives, J, Urgell, E, Espinos, JJ, Tirado, M, Carreras, G, Aulinas, A, Webb, SM, Corcoy, R, Blanco-Vaca, F, Tondo, M
Publicada:
1 mar 2021
Resumen:
The most common form of congenital adrenal hyperplasia (CAH) results from a deficiency of the 21-hydroxylase enzyme (21-OHD), presenting with a broad spectrum of clinical phenotypes according to the CYP21A2 gene mutations. Of the 59 patients with suspected CAH, 62.7% presented a positive genetic result. Of them, 78.4% and 18.9% presented with non-classical and classical forms, respectively. An overall phenotype-genotype correlation of 88.9% was observed. Biochemically, 17-hydroxiprogesterone concentrations were significantly higher in genetically confirmed patients. Genetically, 36 patients presented with previously reported pathogenic variants, and one presented a new variant in homozygosis. Among the 74 alleles tested, point mutations were found in 89.2% and large rearrangements were found in the rest. The most prevalent pathogenic variant was p.(Val282Leu). The inclusion of relatives revealed one further case. Interestingly, 87.5% of relatives were carriers of a pathogenic variant, including two siblings initially classified as genetically positive. In addition, the study of male partners with gestational desire identified several carriers of mild mutations. Studying the allelic distribution of the variants also allowed for reclassifying one patient. In conclusion, a genetic approach including Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) analysis, and allelic distribution of the pathogenic variants represents a beneficial tool for better classifying patients with 21-OHD.
Filiaciones:
Nan, MN:
Hosp Santa Creu & St Pau IIB St Pau, Serv Bioquim, Barcelona 08041, Spain
Roig, R:
Hosp Santa Creu & St Pau IIB St Pau, Serv Bioquim, Barcelona 08041, Spain
Martinez, S:
Hosp Santa Creu & St Pau IIB St Pau, Serv Bioquim, Barcelona 08041, Spain
Rives, J:
Hosp Santa Creu & St Pau IIB St Pau, Serv Bioquim, Barcelona 08041, Spain
Urgell, E:
Hosp Santa Creu & St Pau IIB St Pau, Serv Bioquim, Barcelona 08041, Spain
Espinos, JJ:
Hosp Santa Creu & St Pau IIB St Pau, Serv Ginecol, Barcelona 08041, Spain
Tirado, M:
Hosp Santa Creu & St Pau IIB St Pau, Serv Pediatria, Barcelona 08041, Spain
Carreras, G:
Hosp Santa Creu & St Pau IIB St Pau, Serv Pediatria, Barcelona 08041, Spain
Aulinas, A:
Hosp Santa Creu & St Pau IIB St Pau, Serv Endocrinol, Barcelona 08041, Spain
Univ Vic Univ Cent Catalunya, Fac Med, Vic 08500, Spain
ISCIII, CIBER Enfermedades Raras CIBERER, Madrid 28029, Spain
Webb, SM:
Hosp Santa Creu & St Pau IIB St Pau, Serv Endocrinol, Barcelona 08041, Spain
ISCIII, CIBER Enfermedades Raras CIBERER, Madrid 28029, Spain
Corcoy, R:
Hosp Santa Creu & St Pau IIB St Pau, Serv Endocrinol, Barcelona 08041, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona 08193, Spain
ISCIII, CIBER Bioingn Biomat & Nanomed CIBERBBN, Madrid 28029, Spain
Blanco-Vaca, F:
Hosp Santa Creu & St Pau IIB St Pau, Serv Bioquim, Barcelona 08041, Spain
ISCIII, CIBER Diabet & Enfermedades Metab Asociadas CIBER, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Barcelona 08193, Spain
Tondo, M:
Hosp Santa Creu & St Pau IIB St Pau, Serv Bioquim, Barcelona 08041, Spain
ISCIII, CIBER Diabet & Enfermedades Metab Asociadas CIBER, Madrid 28029, Spain
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