genetic disorder Chapter 5

single gene disorders

are caused by a single gene variant

gene variant

altered protein or decreased protein/enzyme production

autosomal dominant

Marfan syndrome and Huntington disease

autosomal recessive

PKU, Tay-Sachs, sickle cell

X-linked recessive

hemophilia

Marfan Syndrome

gene mutation of extracellular matrix protein abundant in connective tissue (fibrillin - elastic fibers)

•Skeletal abnormalities - long arms where arm span exceeds height, long fingers, hyper-extensible joints

Vision problems

Cardiovascular complications - most life-threatening aspect

Nuerofibromatosis

Causes tumors to develop in the nervous system

•Genetic defect in tumor suppressor gene that regulates cell differentiation and growth

Cutaneous and subcutaneous neurofibromas that develop late in childhood or adolescence

•Café au lait spots - large, flat pigmentations

NF-1

von Recklinghausen disease - neurofibromas in peripheral nerves

NF-2

bilateral acoustic - Schwann cell tumors

•Less common

Phenylketonuria (PKU)

Metabolic disorder - elevated phenylalanine toxic to brain

Deficiency in liver enzyme (PAH): converts phenylalanine to tyrosine

•Phenylalanine from protein rich foods, only use a little, and convert the rest

•Aspartame also contains phenylalanine diet drinks/foods

•Fasting/starvation - triggers muscle catabolism, increasing phenylalanine

•Untreated - intellectual impairment and impaired neurologic development

•Screened at birth

Tay-Sachs disease

Lysosomal storage disorder lack of hydrolytic enzyme leading to increased sphingolipids in nervous tissue (especially brain)

•Leads to destruction of neurons gradual deterioration of motor and mental function

•No treatment: fatal at 4-5 years of age

•1 in 30 persons of Ashkenazi Jewish heritage are carriers

Biologic Females: XX

Homozygous (both X have trait) to show phenotype

•if heterozygous for trait will rarely have phenotype

Biologic Males: XY

only has one X chromosome, so all biologic malesaffected

multifactorial inheritance

Caused by multiple genes and environmental factors (Diabetes, cardiovascular disease, cancer)

chromosomal disorder

Structural Chromosomal Abnormalities• Break in chromosome followed byrearrangement or deletion of parts

Numeric Autosomal

Change in chromosome number of autosome• Down Syndrome - Trisomy 21

Numeric Allosomal

XXY (Klinefelter Syndrome) - 47 chromosomes• 45 X,0 (Turner Syndrome) - 45 chromosomes

Down syndrome

Trisomy 21 - most commonly caused by non-disjunction or error in meiotic cell division• Most common chromosomal disorder• Manifestations• Intellectual disability (variable)• Physical characteristics• Congenital heart defects• Increased risk of• Acute lymphoblastic leukemia• GI malformations

Turner syndrome

Absence of all (45, X0) or part of X chromosome• Clinical features• May vary depending on chromosomalabnormalities• Mosaicism - multiple cell lines• Short stature• Ovarian dysgenesis• May have cardiac abnormalities• Treatment with growth hormone and estrogentherapy

mtDNA disorders

similar causes as nuclear DNA disorders

37 genes

some RNA genes, some genes for cell metabolism/ATP production