title: Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening.
abstract: Steroid 21-hydroxylase deficiency (21-OHD) accounts for more than 90% of congenital adrenal hyperplasia. CAH newborn screening, in general, is based on 17-hydroxyprogesterone dosage (17-OHP), however it is complicated by the fact that healthy preterm infants have high levels of 17-OHP resulting in false positive cases. We report on molecular features of a boy born pre-term (GA = 30 weeks; weight = 1,390 g) with elevated levels of 17-OHP (91.2 nmol/L, normal < 40) upon neonatal screening who was treated as having CAH up to the age of 8 months. He was brought to us for molecular diagnosis. Medication was gradually suspended and serum 17-OHP dosages mantained normal. The p.V281L mutation was found in compound heterozygous status with a group of nucleotide alterations located at the 3' end intron 4 and 5' end exon 5 corresponding to the splice site acceptor region. Molecular studies continued in order to exclude the possibility of a nonclassical 21-OHD form. The group of three nucleotide changes was demonstrated to be a normal variant since they failed to interfere with the normal splicing process upon minigene studies.
authors.affiliation: Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, SP, Brasil.
authors.forename: Fernanda Caroline
authors.initials: FC
authors.lastname: Soardi
authors.forename: Sofia Helena V
authors.initials: SH
authors.lastname: Lemos-Marini
authors.forename: Fernanda Borchers
authors.initials: FB
authors.lastname: Coeli
authors.forename: Víctor Gonçalves
authors.initials: VG
authors.lastname: Maturana
authors.forename: Márcia Duarte Barbosa da
authors.initials: MD
authors.lastname: Silva
authors.forename: Renan Darin
authors.initials: RD
authors.lastname: Bernardi
authors.forename: Giselle Zenker
authors.initials: GZ
authors.lastname: Justo
authors.forename: Maricilda Palandi
authors.initials: MP
authors.lastname: de-Mello
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005189:False Positive Reactions; D005260:Female; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D015997:Neonatal Screening; D011247:Pregnancy; D047928:Premature Birth; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D019326:17-alpha-Hydroxyprogesterone; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase