H28+C insertion in the CYP21 gene: A novel frameshift mutation in a Brazilian patient with the classical form of 21-hydroxylase deficiency

Author(s)

Lau, IF ; Soardi, FC ; Lemos-Marini, SHV ; Guerra, G ; Baptista, MTM ; De Mello, MP

• Document type: Journal article
• Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 86, n. 12, p. 5877-5880, DEC 2001.
• Web of Science Citations: 13

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. (AU)