PMID- 9215318
OWN - NLM
STAT- MEDLINE
DCOM- 19970807
LR  - 20161124
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 82
IP  - 7
DP  - 1997 Jul
TI  - Molecular basis of nonclassical steroid 21-hydroxylase deficiency detected by 
      neonatal mass screening in Japan.
PG  - 2350-6
AB  - Since 1989, neonatal mass screening for congenital adrenal hyperplasia (CAH) has 
      been performed in Japan, and the frequency of the classical form of 
      21-hydroxylase deficiency was found to be nearly identical to that in other 
      countries. However, it has not yet been determined whether our mass screening 
      program can detect the nonclassical (NC) form. From 1991 to 1994, about 4,500,000 
      infants underwent CAH mass screening in Japan. During this period, we identified 
      by screening 2 siblings and 2 unrelated patients who had mild elevation of serum 
      17-hydroxyprogesterone levels at 5 days of age, but who revealed no symptoms of 
      CAH. They were diagnosed as having probable NC steroid 21-hydroxylase deficiency. 
      To clarify the molecular basis of NC CAH detectable by neonatal screening in 
      Japan, the steroid 21-hydroxylase (CYP21) genes from these cases were analyzed. 
      The 2 siblings (patients 1 and 2) had I172N and R356W mutations in 1 allele and 
      in the other allele had local gene conversion, including the P30L mutation in 
      exon 1. Patient 3, who was unrelated, had gene conversion encoding the same P30L 
      mutation in 1 allele and in the other allele had an intron 2 mutation (668-12 
      A-->G), causing aberrant ribonucleic acid splicing, and the R356W mutation. 
      Patient 4, also a compound heterozygote, had the R356W and 707del8 mutations. The 
      estimated rate of detection of the NC form by mass screening (1:1,100,000) seemed 
      low compare to the established detection rate for the classical form (1:18,000). 
      As all of our 4 patients were compound heterozygotes with at least 1 allele 
      bearing 1 or more mutations associated with classic CAH, it may be difficult to 
      detect NC cases carrying only NC-associated alleles using our current neonatal 
      mass screening methods.
FAU - Tajima, T
AU  - Tajima T
AD  - Developmental Endocrinology Branch, National Institute of Child Health and Human 
      Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Fujieda, K
AU  - Fujieda K
FAU - Nakae, J
AU  - Nakae J
FAU - Toyoura, T
AU  - Toyoura T
FAU - Shimozawa, K
AU  - Shimozawa K
FAU - Kusuda, S
AU  - Kusuda S
FAU - Goji, K
AU  - Goji K
FAU - Nagashima, T
AU  - Nagashima T
FAU - Cutler, G B Jr
AU  - Cutler GB Jr
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 68-96-2 (17-alpha-Hydroxyprogesterone)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
SB  - IM
MH  - 17-alpha-Hydroxyprogesterone/blood
MH  - *Adrenal Hyperplasia, Congenital
MH  - Adrenocorticotropic Hormone/pharmacology
MH  - Base Sequence
MH  - Humans
MH  - Infant, Newborn
MH  - Japan
MH  - Mass Screening
MH  - Mutation
MH  - Pedigree
MH  - Sensitivity and Specificity
MH  - Steroid 21-Hydroxylase/*genetics
EDAT- 1997/07/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
AID - 10.1210/jcem.82.7.4094 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1997 Jul;82(7):2350-6. doi: 10.1210/jcem.82.7.4094.