H28+C Insertion in the CYP21 Gene: A Novel Frameshift Mutation in a Brazilian Patient with the Classical Form of 21-Hydroxylase Deficiency

• Published in: The journal of clinical endocrinology and metabolism 2001-12, Vol.86 (12), p.5877-5880
• Main Authors: Lau, Ivy F., Soardi, Fernanda C., Lemos-Marini, Sofia H. V., Guerra Jr, Gil, Baptista, Maria Tereza M., De Mello, Maricilda P.
• Format: Article
• Language: English
• Subjects: Adrenal Hyperplasia, Congenital; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Base Sequence - genetics; Biological and medical sciences; Brazil; DNA Transposable Elements; Endocrinopathies; Female; Frameshift Mutation - genetics; Homozygote; Humans; Infant, Newborn; Medical sciences; Molecular Sequence Data; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Steroid 21-Hydroxylase - genetics; Tropical medicine
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.86.12.8113

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.