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document
Genotyping of CYP21 , linked chromosome 6p markers , and a sex-specific gene in neonatal screening for congenital adrenal hyperplasia . We investigated the feasibility and diagnostic utility of genotyping 9 CYP21 mutations , linked chromosome 6p markers , and a dimorphic X-Y marker from neonatal screening samples . Blood-impregnated filter papers ( Guthrie cards ) from 603 randomly chosen New Zealand neonates were genotyped blind to 17-hydroxyprogesterone ( 17-OHP ) levels . Another 50 samples from Swiss and North American infants with correlative hormonal data were also genotyped . DNA was extracted , and gene-specific PCR was performed . CYP21 PCR products were subjected to ligase detection reaction , simultaneously analyzing 9 CYP21 mutations ; PCR products of other genes were subjected to direct gel analysis . CYP21 genotyping indicated a heterozygote rate of 2.8 % for classic mutations ( excluding CYP21 deletions ) , and 2.0 % for nonclassic mutations in New Zealanders . Ten full-term affected neonates showed a wide range of 17-OHP levels ( 15-1400 nmol/L ) . Sick or preterm infants or infants screened on the first day of life with high 17-OHP proved genetically unaffected . Genetic linkage disequilibrium was found between two CYP21 mutations and chromosome 6p markers . Guthrie cards can be used to accurately genotype CYP21 and other relevant markers , potentially enhancing the specificity and sensitivity of congenital adrenal hyperplasia screening . CYP21 heterozygote frequency for classic mutations is higher than expected based on genotype compared with that predicted by hormonal newborn screening .
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Intervention_Physical
Genotyping of CYP21
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Intervention_Physical
genotyping 9 CYP21
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Intervention_Physical
Blood-impregnated filter papers
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Intervention_Pharmacological
17-hydroxyprogesterone
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Intervention_Pharmacological
CYP21 PCR
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Intervention_Pharmacological
CYP21
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Intervention_Pharmacological
CYP21
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Outcome_Other
feasibility
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Outcome_Other
diagnostic utility
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Outcome_Physical
heterozygote rate
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Outcome_Physical
17-OHP levels
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Outcome_Physical
17-OHP
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Outcome_Physical
Genetic linkage disequilibrium
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Outcome_Physical
CYP21
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Outcome_Other
specificity
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Outcome_Other
sensitivity
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Outcome_Physical
CYP21 heterozygote frequency for classic mutations
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Participant_Age
neonatal
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Participant_Condition
congenital adrenal hyperplasia
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Participant_Age
neonatal
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Participant_Age
neonates
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Participant_Sample-size
Another 50 samples
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Participant_Age
newborn