PMID- 10443693
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20161124
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 8
DP  - 1999 Aug
TI  - A novel missense mutation, GLY424SER, in Brazilian patients with 21-hydroxylase
      deficiency.
PG  - 2870-2
AB  - A previous screening of 17 mutations in 130 Brazilian patients with congenital
      adrenal hyperplasia due to 21-hydroxylase deficiency did not identify mutations
      in 20% of the alleles. To diagnose these alleles we sequenced the entire CYP21
      gene of one Mulatto patient with the simple virilizing form, who had only the
      R356W mutation in a heterozygous state. We identified a heterozygous G-A
      transition in codon 424. This mutation leads to a substitution of glycine by
      serine in a conserved region where glycine is conserved in at least 4 species.
      This novel mutation eliminates 1 of the restriction sites of the BanI enzyme,
      which made its screening possible for the whole series. The G424S mutation was
      found in a compound heterozygous state in 5 families; 4 presented the simple
      virilizing form, and 1 presented the nonclassical form. Interestingly, 3 of 5
      families have a Mulatto origin. This mutation was not identified in 118 CYP21
      alleles of normal individuals, ruling out the possibility of a polymorphism, or
      in 80 pseudogenes, indicating a casual mutagenic event and not a microconversion 
      event. All patients with the G424S mutation presented CYP21P and C4A gene
      deletions and human leukocyte antigen DR17 on the same haplotype, suggesting a
      linkage disequilibrium and a probable founder effect. Search for the G424S
      mutation in other populations will reveal whether it is restricted to the
      Brazilian patients or if it has a wider ethnic distribution.
FAU - Billerbeck, A E
AU  - Billerbeck AE
AD  - Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de Sao Paulo,
      Hospital das Clinicas, Brazil.
FAU - Bachega, T A
AU  - Bachega TA
FAU - Frazatto, E T
AU  - Frazatto ET
FAU - Nishi, M Y
AU  - Nishi MY
FAU - Goldberg, A C
AU  - Goldberg AC
FAU - Marin, M L
AU  - Marin ML
FAU - Madureira, G
AU  - Madureira G
FAU - Monte, O
AU  - Monte O
FAU - Arnhold, I J
AU  - Arnhold IJ
FAU - Mendonca, B B
AU  - Mendonca BB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
SB  - IM
MH  - Adrenal Hyperplasia, Congenital/*genetics
MH  - Female
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - *Mutation, Missense
MH  - Polymerase Chain Reaction
MH  - Steroid 21-Hydroxylase/*genetics
EDAT- 1999/08/12 00:00
MHDA- 1999/08/12 00:01
CRDT- 1999/08/12 00:00
PHST- 1999/08/12 00:00 [pubmed]
PHST- 1999/08/12 00:01 [medline]
PHST- 1999/08/12 00:00 [entrez]
AID - 10.1210/jcem.84.8.5937 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Aug;84(8):2870-2. doi: 10.1210/jcem.84.8.5937.