Heat-transfer-based detection of SNPs in the PAH gene of PKU patients.

[phenylketonuria]

Conventional neonatal diagnosis of phenylketonuria is based on the presence of abnormal levels of phenylalanine in the blood . However , for carrier detection and prenatal diagnosis , direct detection of disease-correlated mutations is needed . To speed up and simplify mutation screening in genes , new technologies are developed . In this study , a heat-transfer method is evaluated as a mutation -detection technology in entire exons of the phenylalanine hydroxylase (PAH ) gene . This method is based on the change in heat-transfer resistance (R (th )) upon thermal denaturation of dsDNA (double -stranded DNA ) on nanocrystalline diamond . First , ssDNA (single -stranded DNA ) fragments that span the size range of the PAH exons were successfully immobilized on nanocrystalline diamond . Next , it was studied whether an R (th ) change could be observed during the thermal denaturation of these DNA fragments after hybridization to their complementary counterpart . A clear R (th ) shift during the denaturation of exon 5 , exon 9 , and exon 12 dsDNA was observed , corresponding to lengths of up to 123 bp . Finally , R (th ) was shown to detect prevalent single -nucleotide polymorphisms , c .473 G >A (R 158 Q ), c .932 T >C (p .L 311 P ), and c .1222 C >T (R 408 W ), correlated with phenylketonuria , displaying an effect related to the different melting temperatures of homoduplexes and heteroduplexes .

Diseases
Validation

Diseases presenting "prenatal diagnosis" symptom

22q11.2 deletion syndrome

achondroplasia

adrenomyeloneuropathy

alexander disease

alpha-thalassemia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

classical phenylketonuria

cohen syndrome

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cystinuria

dentinogenesis imperfecta

epidermolysis bullosa simplex

harlequin ichthyosis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

junctional epidermolysis bullosa

kindler syndrome

krabbe disease

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neonatal adrenoleukodystrophy

oculocutaneous albinism

omenn syndrome

phenylketonuria

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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