--
-- 100 ( (G) (E) (E) (G) G E (Mendelian inheritance) ( ) (autosomal dominant) (Huntington s chorea) ( ) (autosomal recessive) (cystic fibrosis) ( ) (hemophilia) (multifactorial inheritance) ( ) ( ) III-1
(genetic heterogeneity) McKusick 1992 1/50 1/100 1/200 60 (Down syndrome) 3-4 (Turner syndrome) 150 (triploidy) (tetraploidy) (stillbirth) (neonatal death) 6-7 1 ( 0.21 ) 3 ( 0.12 ) (2/1,000) (0.5/1,000) (0.8/1,000) (0.4/1,000) 0.7 0.25 0.05 III-2
Tay-Sachs ) ( ) 10 2-1914 -1954-1966 -1967 83.5 62.5 58.0 50.0 2.0 12.0 8.5 8.9 2.5 2.9 14.5 25.5 31.0 38.2 Madras 1976 95 5 III-3
10 20 1 1/4 (1) (2) (3) (congenital hypothyroidism) (hemoglobino pathesis) (α-antitrypsin deficiency) (Duchenne III-4
muscular dystrophy) 1960 Guthrie 1962 (bacterial inhibition assay) (phenylketonuria) (maple syrup urine disease) (histidinemia) (galactosemia) (homocystinuria) 1970 Dussault 1974 (radioimmunoassay) 1:4,000-1:5,000 1:13,000 1:50,000 1:170,000 1:200,000 III-5
III-6
(thyroxine T4) (congenital hypothyroidism) 1/3,000 ( ) 1 (athyreosis) 2 (thyroid hypoplasia) 3 (ectopic thyroid) ( ) ( ) 1/50,000 1/150,000 III-7
( ) (transient congenital hypothyroidism) 1 2 3 4 (L-thyroxine) (thyroid stimuiating hormone TSH) 10 mu/l blood 10 mu/l ( ) ( ) ( ) ( )thyroid sonogram 99m Tc thyroid scan( ) III-8
1934 Dr. Folling (phenylpyruvic acid) 1937 (phenylketonuria PKU) (phenylalanine Phe) (hydroxylation) (tyrosine Tyr) 酶 酶 (phenylalanine hydroxylase PAH) 酶 (Gtp cyclohydrolase I GTPCHI) 酶 (6-pyruvoyl tetrahydropterin synthase PTPS) 酶 (dihydropteridine reductase DHPR) 酶 (pterin-4α-carbinolamine dehydratase PCD) 酶 (PAH) PKU 98 99% PKU 70 80% 酶 (tetrahydrobiopterin BH4) ( ) 酶 PKU 20% 30% III-9
PKU 95 85 53-45 BH4 PKU ( ) PKU 4-8 mg/dl (maternal PKU) ( ) ( 酶 酶 酶 ) BH4(1-5 mg/kg/day) 4mg/dL L-dopa (5-15 mg/kg/day) 5-hydroxy tryptophan (4-10 mg/kg/day) carbidopa(1-2 mg/kg/day) ( ) 酶 BH4 folinic acid PKU 2 mg/dl blood ( 48 ) PKU III-10
( ) ( ) ( ) (GC/Mass) ( ) (HPLC) (neopterin N) 酶 (biopterin B) B%=[B/(B+N)] 100% ( ) DHPR ( )BH4 (BH4 loading test) BH4 (7.5 mg/kg) 4-6 2 mg/dl BH4 (responsive) BH4 (nonresponsive) PKU ( ) PKU B% ( ) BH4 DHPR ( )GTPCHI PKU B% N BH4 DHPR ( )PTPS SR PKU B% 5% BH4 DHPR ( )DHPR PKU B% 80% BH4 DHPR ( )PCD PKU 7- (7-biopterin) III-11
(homocystinuria) 酶 (cystathionine-β-synthase) (homocysteine) (cystine Cys) (methionine Met) (homocystine Hcy ) (Mix disulfide) B6(VitB6) (betain) B6 B6 B12 (folic acid) B6 1000 mg/day 1 mg/dl blood 酶 III-12
(galactosemia) (galactose) (glucose) 酶 酶 (galactokinase) -1- 苷 酶 (galactose-1-phosphate uridyltransferase) 苷 -4- 酶 (UDP galactose-4-epimerase) -1- 苷 酶 -1- 苷 酶 酶 苷 -4- 酶 AL 110-1- (galactose-1-phosphate) galactitol (galactose-1-phosphate uridyl- transferase ) ( ) ( Uridine) III-13
-1-8 mg/dl blood -1- -1- 酶 -1- 苷 酶 III-14
- - 酶 - - 酶 (glucose-6-phosphate dehydrogenase G6PD) (X-link) G6PD 酶 苷肽 (Glutathione, G-SH) G6PD G-SH G6PD 2% G6PD G6PD ( ) ( ) G6PD 萘 ( ) G6PD G6PD 20% (Heterozygote) G6PD ( ) 80% G6PD III-15
" "(genetic counseling) 1947 (Reed) " " " " III-16
" (clinical geneticist) (PhD medical geneticist) (clinical cytogeneticist) (clinical biochemical geneticist) (genetic counselor) ( " ") ( ) III-17
( ) ( ) ( ) ( ) -- III-18
III-19
( ) ( ) " "(forme fruste) " "(forme tardive) " " " " " " ( ) III-20
" " " III-21
III-22
( ) ( ) III-23
1992;91(3):S183-6 : 1987 : 199l 1982;23:31-5 : 1985;26:542-7 : 1970;11:163-5 Bergsma D:Birth Defects and Compendium, 2nd ed. New York:Alan R Liss, 1979:1-1122 Emery AEH, Rimoin DL:Principles and Practice of Medical Genetics, 2nd ed.edinburgh:churchill Livingstone,1990:1-2035. III-24
Fuhrmann W, VogeI F:Genetic Counseling, 3rd ed New York:Springer-Verlag, 1983:1-374. HarPer PS:Practical Genetic Counselling, 3rd ed. London:Wright, 1988:1-489. Murphy EA, Chase GA:Principles of Genetic Counselng. Chicago: Year Book Medical Publishers, 1975:1-476. III-25