Designer Genes Diseases

Cystic Fibrosis

• Gene: CFTR

• Mutation Type: 3-bp deletion (ΔF508)

• Inheritance: Autosomal recessive

• Diagnosis: PCR, sequencing, gel electrophoresis

Sickle Cell Disease

• Gene: HBB

• Mutation Type: Missense point mutation (Glu→Val)

• Inheritance: Autosomal recessive

• Diagnosis: Restriction digest + gel, sequencing

Tay-Sachs Disease

• Gene: HEXA

• Mutation: Frameshift; enzyme deficiency

• Inheritance: Autosomal recessive

• Diagnosis: HexA enzyme assay; HEXA testing

Phenylketonuria (PKU)

• Gene: PAH

• Mutation: Loss-of-function

• Inheritance: Autosomal recessive

• Diagnosis: Newborn screen; PAH gene test

Huntington’s Disease

• Gene: HTT

• Mutation: CAG repeat expansion

• Inheritance: Autosomal dominant

• Diagnosis: CAG repeat test

Marfan Syndrome

• Gene: FBN1

• Mutation: Missense/dominant-negative

• Inheritance: Autosomal dominant

• Diagnosis: Clinical + FBN1 sequencing

Achondroplasia

• Gene: FGFR3

• Mutation: Gain-of-function point mutation

• Inheritance: Autosomal dominant

• Diagnosis: FGFR3 test

Neurofibromatosis Type I

• Gene: NF1

• Mutation: Loss-of-function

• Inheritance: Autosomal dominant

• Diagnosis: Clinical + NF1 sequencing

Duchenne Muscular Dystrophy

• Gene: DMD

• Mutation: Frameshift deletion

• Inheritance: X-linked recessive

• Diagnosis: MLPA (copy number test)

Hemophilia A

• Gene: F8

• Mutation: Inversions, point mutations

• Inheritance: X-linked recessive

• Diagnosis: Factor VIII assay + DNA test

Hemophilia B

• Gene: F9

• Mutation: Point mutations

• Inheritance: X-linked recessive

• Diagnosis: Factor IX assay

Fragile X Syndrome

• Gene: FMR1

• Mutation: CGG repeat expansion

• Inheritance: X-linked dominant

• Diagnosis: Repeat expansion test

Rett Syndrome

• Gene: MECP2

• Mutation: Loss-of-function

• Inheritance: X-linked dominant

• Diagnosis: MECP2 sequencing

G6PD Deficiency

• Gene: G6PD

• Mutation: Missense

• Inheritance: X-linked recessive

• Diagnosis: Enzyme assay

Alpha-1 Antitrypsin Deficiency

• Gene: SERPINA1

• Mutation: Misfolded protein

• Inheritance: Codominant

• Diagnosis: A1AT levels + genetic test

Maple Syrup Urine Disease (MSUD)

• Gene: BCKDHA, BCKDHB

• Mutation: Enzyme deficiency

• Inheritance: Autosomal recessive

• Diagnosis: Newborn screening

Galactosemia

• Gene: GALT

• Mutation: Loss-of-function

• Inheritance: Autosomal recessive

• Diagnosis: Newborn screen

Homocystinuria

• Gene: CBS

• Mutation: Loss-of-function

• Inheritance: Autosomal recessive

• Diagnosis: Homocysteine level; sequencing

Down Syndrome

Gene: Chromosome 21
Mutation Type: Trisomy (Trisomy 21)
Inheritance: Nondisjunction (not inherited)
Diagnosis: Karyotype, NIPT

Edwards Syndrome

Gene: Chromosome 18
Mutation Type: Trisomy (Trisomy 18)
Inheritance: Nondisjunction
Diagnosis: Karyotype

Patau Syndrome

Gene: Chromosome 13
Mutation Type: Trisomy (Trisomy 13)
Inheritance: Nondisjunction
Diagnosis: Karyotype

Turner Syndrome

Gene: X Chromosome
Mutation Type: Monosomy (XO)
Inheritance: Nondisjunction
Diagnosis: Karyotype

Klinefelter Syndrome

Gene: X Chromosome
Mutation Type: Aneuploidy (XXY)
Inheritance: Nondisjunction
Diagnosis: Karyotype

Cri-du-Chat Syndrome

Gene: Chromosome 5
Mutation Type: 5p deletion
Inheritance: Usually de novo
Diagnosis: FISH, microarray

Prader–Willi Syndrome

Gene: 15q11–13 (paternal)
Mutation Type: Paternal deletion / imprinting defect
Inheritance: Imprinting
Diagnosis: Methylation test

Angelman Syndrome

Gene: 15q11–13 (maternal)
Mutation Type: Maternal deletion / imprinting defect
Inheritance: Imprinting
Diagnosis: Methylation test

LHON

Gene: mtDNA
Mutation Type: Point mutation
Inheritance: Maternal
Diagnosis: mtDNA sequencing

MELAS

Gene: mtDNA
Mutation Type: tRNA mutations
Inheritance: Maternal
Diagnosis: mtDNA sequencing

Hereditary Breast/Ovarian Cancer (BRCA1/BRCA2)

Gene: BRCA1 or BRCA2
Mutation Type: Loss-of-function
Inheritance: Autosomal dominant
Diagnosis: BRCA sequencing

Retinoblastoma

Gene: RB1
Mutation Type: Loss-of-function (two-hit)
Inheritance: Autosomal dominant
Diagnosis: RB1 gene sequencing

Li-Fraumeni Syndrome

Gene: TP53
Mutation Type: Loss-of-function
Inheritance: Autosomal dominant
Diagnosis: TP53 sequencing

Chronic Myelogenous Leukemia (CML)

Gene: BCR-ABL fusion
Mutation Type: t(9;22) translocation
Inheritance: Not inherited (somatic)
Diagnosis: PCR for BCR-ABL, FISH