title: H28+C insertion in the CYP21 gene: a novel frameshift mutation in a Brazilian patient with the classical form of 21-hydroxylase deficiency.
abstract: In the classical form of 21-hydroxylase deficiency, CYP21- affected genes either carry mutations present in the CYP21P pseudogene (microconversions) or bear a chimeric gene that replaces the active gene as a result of large conversion or deletion mutational events. Previous genotyping of 41 Brazilian patients revealed 64% microconversion, whereas deletions and large gene conversions accounted for up to 21% of the molecular defect. The present paper describes a new mutation disclosed by sequencing an entire gene in which no pseudogene-originated mutation had been found. The patient with the classical form of 21-hydroxylase deficiency is the daughter of a consanguineous marriage, and she is homozygous for a novel frameshift H28+C within exon 1. The mutation causes a stop codon at amino acid 78. Both parents are heterozygous for the mutation as confirmed by allele-specific oligonucleotide PCR. The H28+C is not present in the published CYP21P sequences and is likely to result in an enzyme with no activity.
authors.affiliation: Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, São Paulo, Brazil.
authors.forename: I F
authors.initials: IF
authors.lastname: Lau
authors.forename: F C
authors.initials: FC
authors.lastname: Soardi
authors.forename: S H
authors.initials: SH
authors.lastname: Lemos-Marini
authors.forename: G
authors.initials: G
authors.lastname: Guerra
authors.forename: M T
authors.initials: MT
authors.lastname: Baptista
authors.forename: M P
authors.initials: MP
authors.lastname: De Mello
mesh_terms: D000312:Adrenal Hyperplasia, Congenital; D001483:Base Sequence / Q000235:genetics; D001938:Brazil; D004251:DNA Transposable Elements; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D013255:Steroid 21-Hydroxylase