H28+C insertion in the CYP21 gene: a novel frameshift mutation in a Brazilian patient with the classical form of 21-hydroxylase deficiency.
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.
Lau
I F
IF
Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, São Paulo, Brazil.
Soardi
F C
FC
Lemos-Marini
S H
SH
Guerra
G
G
Baptista
M T
MT
De Mello
M P
MP
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*
D004251:DNA Transposable Elements; D013255:Steroid 21-Hydroxylase