The use of the polymerase chain reaction in prenatal diagnosis of growth hormone gene deletions.
OBJECTIVE
Familial isolated growth hormone deficiency (IGHD) type IA is characterized by a complete absence of human growth hormone (hGH) resulting in most cases from either a 6.7 or 7.7 kb deletion of DNA containing the hGH-1 gene. These patients have a strong initial anabolic response to exogenous recombinant hGH (r-hGH) therapy, frequently associated with the development of immune intolerance to r-hGH which causes an arrest of response to r-hGH replacement. This disorder is inherited as an autosomal recessive trait.


METHODS
In two pregnancies at risk, the polymerase chain reaction (PCR) was applied as a method for identifying hGH-1 gene deletions in DNA obtained by chorionic villus sampling (CVS) in the first trimester.


RESULTS
Homozygotes for the 6.7kb deletion of DNA containing the hGH-1 gene were easily and conclusively detected by the absence of 1900, 761 and 712bp fragments after SmaI digestion of the polymerase chain reaction products. In contrast, the pattern found in heterozygotes for the hGH-1 gene deletion was difficult to distinguish from the pattern found in normal homozygotes.


CONCLUSIONS
We conclude that the polymerase chain reaction method is valuable for diagnosing individuals who are homozygous for hGH-1 gene deletions, while heterozygotes and normal individuals may be difficult to distinguish from each other. We suggest that, in these cases, Southern blotting remains the analysis to perform.
Mullis
P E
PE
University of Bern, Department of Paediatrics, Inselspital, Switzerland.
Brickell
P M
PM
D015139:Blotting, Southern; D002648:Child; D002824:Chorionic Villi; D002869:Chromosome Aberrations / Q000175:diagnosis*; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D005260:Female; D013006:Growth Hormone / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
D013006:Growth Hormone