TABLE 1: Inherited diseases with genetic tests used in clinical practice that were classified as having more public health impact: Newborn screening
Biotinidase deficiency |
BTD |
AR |
1.6/100,000 |
|
Congenital adrenal hyperplasia |
CYP21A2 (CYP21) |
AR |
6.7/100,000 |
|
Congenital hypothyroidism |
FOXE1 (FKHL15), FKHL15,
PAX8, TSHR |
AR |
1/50,000 |
|
Cystic fibrosis |
ABCC7 (CFTR) |
AR |
1/3,900 (white); 1/17,000 (black) |
|
Fatty acid oxidation disorder
unspecified |
ACADM, HADHB,
ACADVL, ACADS |
AR |
Rare |
|
Galactokinase deficiency |
GALK1 |
AR |
|
1/50,000–1/100,000 |
Galactosemia |
GALE, GALT |
AR |
|
1/30,000 |
Glucose-6-phosphate dehydrogenase
deficiency |
G6PD (many variants) |
XL |
10% American black males |
|
Glutaricacidemia type I |
GCDH |
AR |
Rare |
|
Glutaricacidemia type II |
ETFA, ETFB, ETFDH |
AR |
Rare |
|
Hemoglobin C; sickle cell disease |
HBB |
AR |
1/835 (African American) |
|
Hemoglobin S; sickle cell disease |
HBB |
AR |
1/375 (African American); 1/100,000 (white) |
|
Homocystinuria |
CBS |
AR |
1/200,000–1/335,000 |
|
Maple syrup urine disease (MSUD) |
BCKDHA, BCKDHB, DBT |
AR |
1/185,000 |
1/176 (Mennonite) |
Medium chain acyl-coenzyme A
dehydrogenase deficiency (MCAD) |
ACADM |
AR |
1/10,000 |
|
Propionic acidemia |
PCCA, PCCB |
AR |
Rare |
|
Short chain acyl-coA dehydrogenase
deficiency (SCAD) |
ACADS |
AR |
Rare |
|
Very long chain acyl-coA
dehydrogenase deficiency (VLCAD) |
ACADVL |
AR |
Rare |
|
Long chain 3-hydroxyacyl coA
dehydrogenase (LCHAD) |
HADHA, HADHB |
AR |
1/50,000 |
|
Note: The prevalence figures come from many sources, and although they appeared to be the best estimate available, their accuracy could not be validated.
a Mode of inheritance: AR, autosomal recessive; XL, X linked.
TABLE 2: Inherited diseases with genetic tests used in clinical practice that were classified as having more public health impact: Other population screening
Alkaptonuria |
HGD |
AR |
|
4/100,000 |
α thalassemia |
HBA1, HBA, HBZ |
AR |
Significant in Southeast Asian populations |
|
β thalassemia |
HBB |
AR |
Carrier prevalence of 12–14% in
Mediterranean populations |
|
Bloom syndrome |
BLM |
AR |
Rare (screening for Ashkenazi) |
|
Canavan disease |
ASPA |
AR |
15.6/100,000 (Ashkenazi) |
|
Down syndrome critical region |
DCR |
AR |
|
1/800 |
Gaucher disease |
GBA |
AR |
1/600–2,500 |
|
Niemann-Pick disease due to
sphingomylinase |
SMPD1(ASM) |
AR |
1/40,000 (Ashkenazi) |
|
Tay-Sachs disease |
HEXA |
AR |
|
1/3,600
(Ashkenazi) |
Note: The prevalence figures come from many sources, and although they appeared to be the best estimate available, their accuracy could not be validated.
a Mode of inheritance: AR, autosomal recessive; AL, autosomal loci not specified.
TABLE 3: Inherited diseases with genetic tests used in clinical practice that were classified as having more public health impact: Common diseases (>1/2,000 prevalence)
Azoospermia (Y chromosome microdeletion panel) |
AZF1, AZF2, DAZ,
RBMY1A1(RBM1|RBM2|
YRRM1) |
YL |
20% of men who seek help at infertility
clinics present with nonobstructive
oligospermia or azoospermia |
|
BRCA1 hereditary breast cancer |
BRCA1 |
AD |
10–20/10,000 |
|
BRCA2 hereditary breast cancer |
BRCA2 |
AD |
5–10/10,000 |
|
Congenital bilateral absence of the vas deferens |
ABCC7 (CFTR) |
AR |
2% of men with obstructive
azoospermia |
|
Coronary artery disease risk factor (ACE) |
ACE |
AD |
CAD is leading cause of death in the
United States |
|
Coronary artery disease risk factor (PLA1/2) |
ITGB3 |
AD |
As above |
|
Diabetes mellitus, non–insulin-dependent |
GPD2, MAPK8IP1, IB1, PPAR-gamma |
AD |
6/1,000 |
|
Factor V Leiden thrombophilia |
F5 |
AD |
|
1/1,000 symptomatic venous thrombosis |
Familial adenomatous polyposis (APC) |
APC |
AD |
6/100 (Ashkenazi) |
|
Familial colorectal cancer |
APC |
AD |
|
134,000 new cases of colorectal cancer in
US in 1996 |
Familial combined hyperlipidemia |
APOE |
AD |
2/1,000 |
|
Fragile X syndrome (FMR1) |
FMR1 (FRAXA) |
XL |
1/1,250 (males); 1/2,500 (females) |
|
Hereditary hemochromatosis (HFE) |
HFE |
AR |
3/1,000 |
|
Hereditary nonpolyposis colon cancer |
MLH1, MSH2, MSH6, PMS1,
PMS2, TGFBR2 |
AL |
2/1,000 |
|
Late-onset familial Alzheimer disease |
AD5, APOE |
AD |
10% of persons >70 years have
significant memory loss and >50%
of these have Alzheimer disease |
|
MTHFR thermolabile variant |
MTHFR |
AR |
30–40% of French Canadians |
|
Multiple endocrine neoplasia type I (MEN1) |
MEN1 |
AD |
|
100,000 in US develop
hyperparathyroidism |
Nonsyndromic hereditary hearing loss and deafness
(connexin 26) |
GJB2 (CX26|DFNA3| DFNB1) |
AL |
|
1/1,000 for hearing loss with 50% being
syndromic, leaving 50% for potential
testing |
Nonsyndromic hereditary hearing loss and deafness
(mitochondrial) |
MTRNR1, MTTS1 |
MT |
|
As above |
Oculopharyngeal muscular dystrophy |
PABP2 |
AL |
|
1/1,000 in some ethnic groups |
Polycystic kidney disease, dominant |
PKD1, PKD2, PKD3 |
AD |
|
1/400–1/1,000 |
Preeclampsia |
AGT, PEE1 |
AD |
Affects 2–4% of pregnancies |
|
Prothrombin G20210A thrombophilia |
F2 |
AD |
|
1/1,000 symptomatic venous thrombosis |
Note: The prevalence figures come from many sources, and although they appeared to be the best estimate available, their accuracy could not be validated.
a Mode of inheritance: AD, autosomal dominant; AR, autosomal recessive; XL, X linked; YL, Y linked; AL, autosomal loci not specified; MT, mitochondrial.
TABLE 4: Inherited diseases with genetic tests used in research that would be classified as having more public health impact if used clinically
Abdominal aortic
aneurysm |
COL3A1 |
AD |
150/10,000 (males > 50 years) |
|
Alcoholism |
Unknown |
AD |
14 million Americans abuse alcohol or are
alcoholics |
|
Bipolar disorder |
MAFD1 |
AL |
1–2% population |
|
Diabetes mellitus, MODY
types 5, 4, 3, 2, 1 |
TCF2 (HNF1 beta), IPF1, TCF1
(HNF1A), GCK, HNF4A |
AR |
1 million+ people in US diagnosed |
|
Factor XI deficiency |
F11 |
AD |
1/190 (Ashkanazi) |
|
Familial
hypercholesterolemia |
APOBLDLR |
AD |
1/500 (heterozygotes)
1/1,000,000 (homozygotes) |
|
Familial
hyperparathyroidism |
HRPT2, MEN1 |
AD |
1/1,000 |
|
Glaucoma, dominant
(adult onset) |
GLC1B, GLC1C, GLC1D,
GLC1E, GLC1F |
AL |
Age-dependent:
0.5% in 60s
3% in 70s
14% ≥80 |
|
Multiple sclerosis |
MS |
AD |
2,500,000 (worldwide) |
|
Neural tube defect |
Unknown |
AD |
|
1/1,000 |
Noonan syndrome |
NS1 |
AD |
|
1/1,000 worldwide |
Oculocutaneous albinism |
TYR, OCA2(P), TYRP1 |
AR |
1/20,000 in most populations, giving a
heterozygote frequency of 1/70 |
1/10,000 in African Americans, 1/
227–240 in some Amerindian
populations |
Otosclerosis |
OTSC1 |
AD |
1/330 (Caucasians); 1/3,300 (African Americans) |
|
Parkinson disease |
SNCA (PARK1) |
AD |
10–35/10,000 |
|
Premature ovarian failure |
DIAPH2 (POF1) |
AD or XL |
1% of women <40 years |
|
Prostate cancer |
HPC1, HPCX, PCAP (HPC2) |
AL or XL |
|
100,000+ cases in US per year |
Psoriasis |
PSORS1, PSORS2, PSORS3 |
AD |
1–2% of population |
|
Schizophrenia |
SCZD1-7 |
AL |
1% of the population develops schizophrenia
during their lifetime |
|
Note: The prevalence figures come from many sources, and although they appeared to be the best estimate available, their accuracy could not be validated.
a Mode of inheritance: AD, autosomal dominant; AR, autosomal recessive; XL, X linked; AL, autosomal loci not specified.
|
|