Genetics Textbook Diseases

Front 1

What are the genetics of Achondroplasia?

Back 1

Autosomal dominant
Mutation in the FGFR3 receptor, mutations increase with paternal age.

Front 2

What mutation occurs in Achondroplasia and what is the result?

Back 2

FGFR3 (fibroblast receptor defect).
Leads to constitutive osteoclast activity which causes short arm/legs, macrocephaly, spinal cord compression, normal IQ, hyperflexible joints and hydrocephalus.

Front 3

How do you diagnose achondroplasia? Treatment? What is specific to the disease?

Back 3

Radiographic test of dwarf and DNA test for FGFR mutation.
Surgical intervention for hydrocephalus and spinal cord compression. Growth hormone for height.
Specific to this disease: Worsens with advanced paternal age.

Front 4

What are the genetics of familial breast cancer?

Back 4

Autosomal dominant. Mutation in the BRCA1 and BRCA2 genes

Front 5

What mutation occurs in Familial breast cancer and what is the result?

Back 5

BRCA1 and BRCA2 mutation which are tumor suppressor genes.
BRCA1 mutations have increased risk for breast, ovarian, prostate and colon cancer.
BRCA2 have increased risk for male and female breast, ovarian, prostate, GB and pancreatic cancer.

Front 6

What is the treatment for familial breast cancer?

Back 6

Prevention: Yearly mammograms and male prostate exams. Bilateral mastectomy and salpingo-oophorectomy reduces cancer by 90%.

Front 7

What is specific to familial breast cancer?

Back 7

Founder effect and tumor suppressor gene

Front 8

What are the genetics of chronic myelogenous leukemia?

Back 8

No germline involvement.
Translocation of the abl gene (9) to brc gene (22) resulting in a Philadelphia chromosome.

Front 9

What mutation occurs in CML and what is the result?

Back 9

9-22 translocation to form Philadelphia chromosome. BCR/ABL gene is an oncogene which produces the bcr/abl protein product that causes cell division and proliferation.

Front 10

Symptoms of CML?

Back 10

Fatigue, malaise, weight loss and splenomegaly. Millions of blast cells in peripheral blood.

Front 11

How do you diagnose CML? Treatment?

Back 11

Diagnosis made with chronic phase blast count in peripheral blood.
Treatment: Imatinib which replaces ATP on bcr/abl protein product inactivating it. Bone marrow transplant. Finally, α-interferon which suppresses the bone marrow.

Front 12

What type of gene is the bcr/abl gene?

Back 12

Oncogene

Front 13

What are the oncogenes that we should know?

Back 13

BCR/ABL, RAS, MYC and RET

Front 14

What are the tumor suppressor genes that we should know?

Back 14

Rb, P53, APC, BRCA1 and BRCA2

Front 15

What are the genetics of cystic fibrosis?

Back 15

Autosomal recessive. Trinucleotide deletion of region coding for Phe residue on chromosome 7 (∆F508)

Front 16

What is the mutation in cystic fibrosis and what does it cause?

Back 16

Trinucleotide deletion of Phe residue (7) which codes for cystic fibrosis transmembrane receptor (CFTR).
W/o the CFTR, secretions are very thick due to no NaCl. As a result lung infections and pancreatitis occur often.
Sweat is also very salty because the NaCl pump is reversed in the skin so NaCl can't be reabsorbed.

Front 17

What are the symptoms of CF?

Back 17

Begins with meconium ileus, poor growth, COPD, chronic infections and malnutrition.
Wolffian ducts fail to develop which causes azoospermia in 95% of males.

Front 18

What is diagnosis and treatment for CF?

Back 18

Sweat test is diagnostic
Treatment: Constant pulmonary clearance, management of infections, preventing intestinal obstruction and lung transplant.

Front 19

What is associated with pancreatic insufficiency in CF patients?

Back 19

The ∆F508 mutation is closely assoc. with PI.

Front 20

What are the genetics of Duschenne's muscular dystrophy?

Back 20

X-linked recessive. The mutation is in the DMD gene which codes for dystrophin. Dystrophin is a protein that stablizes the sarcolemma.

Front 21

What are the symptoms of DMD?

Back 21

Presents btw 3-5yrs old with hypotonia and muscle weakness. At age 5, Gower's sign presents with calf pseudohypertrophy. At age 12, they are confined to a wheelchair with scoliosis. 95% of patients have cardiac defects.

Front 22

Diagnosis for DMD? Treatment?

Back 22

Muscle biopsy and test for dystrophin protein. DNA test for DMD mutation.
Treatment: No cure. Reduce muscle contractures, maintain mobility, monitor cardiac and pulmonary function.

Front 23

What are the genetics of familial adenomatous polyposis?

Back 23

Autosomal dominant with mutation in the APC gene. APC protein is a tumor suppressor gene involved in cell proliferation and division.
Loss of APC function leads to increased levels of β-catenin which stimulates transcription of other genes.

Front 24

T/F Mutations in both alleles of APC gene causes FAP?

Back 24

False. Technically, you need mutations in other cell division genes to cause cancer.
Mutations in both alleles of APC causes polyp formation

Front 25

Presentation of FAP?

Back 25

Formation of hundreds of polyps in the colon early in life. Some of these will develop into cancer.

Front 26

Diagnosis and treatment of FAP?

Back 26

Individuals with >100 polyps or btw 10-100 with family history of FAP are diagnosed.
Treatment: Regular colonoscopies and eventually a colectomy with ileoanal pullthrough.

Front 27

What type of gene is the FAP gene?

Back 27

Tumor suppressor gene.

Front 28

What are the genetics of fragile X syndrome?

Back 28

X-linked with trinucleotide repeat (CGG) mutation in FMR gene. Mutations decrease with paternal transmission and increase with maternal transmission.

Front 29

What is the mutation in fragile X and what does it do?

Back 29

Loss of function mutation in FMR gene which normally codes for chaperone protein to take mRNA from nucleus to ribosomes.

Front 30

Symptoms of fragile X?

Back 30

Male: Severe behavioral problems, mild mental retardation, hyperactivity and autism. Large head, long face and MACRO-ORCHIDISM.

Front 31

What disease is characterized by macro-orchidism?

Back 31

Fragile X syndrome

Front 32

What is diagnosis and treatment of fragile X syndrome?
What is specific to the disease?

Back 32

DNA tests done when symptoms suggest
Treatment: Control the bad behavior.
GENETIC ANTICIPATION

Front 33

What are the genetics of hemophilia?

Back 33

X-linked recessive. Mutation in F8C gene or F9 gene causes deficient factor 8 in hemophilia A and factor 9 in hemophilia B.

Front 34

Symptoms of hemophilia, diagnosis and treatment?

Back 34

Severe case: Bleeding into joints, soft tissue and muscles. Minor head contusions cause cephalohematomas.
Mild case: Prolonged bleeding after trauma or surgery.
Diagnosis: Measure factor 8 or 9 levels in the blood.
Treatment: Replace missing factors.

Front 35

What are the genetics of hereditary non-polyposis colon cancer?

Back 35

Autosomal dominant disorder with mutation in DNA repair genes. 90% have micro-satellite instability.

Front 36

What is the result of the mutations in HNPCC?

Back 36

DNA mismatch repair usually reduces mutations by 1000 fold. Missing mismatch repair causes huge increase in cancer risk.

Front 37

Symptoms of HNPCC? Treatment?

Back 37

Similar rate of polyp formation compared the normal population except occur much earlier in life. Almost all polyps form proximal to splenic flexure.
Treatment: Regular colonoscopies from age 25 on. Women get regular ultrasounds for ovarian or endometrial cancer.

Front 38

What is specific to HNPCC?

Back 38

Micro-satellite instability.

Front 39

What are the genetics of huntington's disease?

Back 39

Autosomal dominant trinucleotide repeat (CAG). CAG repeat leads to polyglutamine tract in Huntingtin protein.
Huntingtin protein has unknown function but gain of function causes neostriatal and brain atrophy.

Front 40

Symptoms of Huntington's disease? Diagnosis? Treatment?

Back 40

30% of people have psychiatric problems.
66% of people have cognitive and motor problems.
90% of people have chorea.
Diagnosis: DNA test
Treatment: Blocking the gene product in mice has shown promise.

Front 41

What is specific to Huntington's disease? What is difference between it and Fragile X?

Back 41

GENETIC ANTICIPATION like Fragile X but this time paternal transmission increases the number of mutations and maternal decreases it.

Front 42

What are the genetics of Marfan's syndrome?

Back 42

Autosomal dominant mutation in fibrillin gene. Fibrillin protein is load-bearing protein in structures like the zonular fibers of the lens, aorta and skin.

Front 43

Symptoms of Marfan's syndrome? Diagnosis? Treatment?

Back 43

MASS - Mitral valve prolapse, aortic dissection, skeletal deformities, skin problems and lens dislocation.
Diagnosis: Symptoms often lead to diagnosis, DNA test not available.
Treatment: Manage abnormalities with surgical and medical intervention.

Front 44

What are the genetics of Miller-Dieker syndrome?

Back 44

80% new mutation. 20% inherited balanced translocation. This mutation is a LIS1 gene hemizygous deletion

Front 45

What does the missing protein normally do in Miller Dieker syndrome?

Back 45

LIS1 protein usually helps with neuronal migration. W/o, you develop Lissencephaly (smooth gyri) which is where it gets it's name from.

Front 46

What are the symptoms of Miller-Dieker syndrome?

Back 46

Lissencephaly (smooth or few gyri), brain dysgenesis, hypotonia, failure to thrive and death before 2 yrs of age.

Front 47

Diagnosis of Miller-Dieker syndrome? Treatment?

Back 47

MRI findings of smooth gyri. FISH test for chromosome 17 LIS1 gene deletion.
Treatment: NG tube for feeding and pharmacological treatment for seizures.

Front 48

What are the genetics of myoclonic epilepsy with ragged red fibers?

Back 48

Mitochondrial inheritance. Deletion in genes coding for complex I and IV.
mtDNA more prone to mutations do to exposure to high levels of ROS.

Front 49

What are the symptoms for myoclonic epilepsy with ragged red fibers? What is the diagnosis?

Back 49

Presents with worsening epilepsy and muscle weakness as mutations in mtDNA worsen with exposure to ROS.
Diagnosis: Muscle biopsy looking for ragged red fibers.

Front 50

What is treatment for myoclonic epilepsy with ragged red fibers? What is specific for this disease?

Back 50

Treatment: Vitamins to improve ox.phos.
MITOCHONDRIAL INHERITANCE.

Front 51

What are the genetics of non-syndromic deafness?

Back 51

Autosomal dominant and recessive.
Mutation in the GfB2 gene which normally codes for an ion channel in the cochlea.

Front 52

What are the symptoms of non-syndromic deafness?

Back 52

The dominant condition presents with deafness later on in life and with hyperkeratosis of the palms and soles.

Front 53

Diagnosis of non-syndromic deafness? Treatment?

Back 53

DNA test to differentiate between syndromic and non-syndromic deafness
Treatment: Cochlear implant
Newborn screening of non-syndromic deafness is now done.

Front 54

What are the genetics of Prader-Willi syndrome?

Back 54

Autosomal dominant if due to imprinting. Caused by a mutation in chromosome 15 of paternal chromosome leaving only maternally imprinted 15.
Can also result from maternal disomy in which case paternal 15 is missing.

Front 55

What are the symptoms of Prader-Willi? Diagnosis?

Back 55

Infant: Hypotonia, feeding difficulties, hypogonadism and cryptorchidism.
Adolescent: Feeding difficulty flips to overeating and obesity. Also have infertility, behavior problems and MR.

Front 56

What is the diagnosis for Prader-Willi? Treatment?

Back 56

DNA test for maternally imprinted chromosome 15.
Treatment: Restrict diet, provide sex hormones for development but this worsens male behavior and predisposes the females to stroke.

Front 57

What is specific for Prader-willi?

Back 57

Genetic imprinting

Front 58

What are the genetics for Retinoblastoma?

Back 58

Autosomal dominant disorder with RB suppressor gene mutation. RB protein normally sequesters transcription factors for cell division.

Front 59

What are the symptoms of retinoblastoma? Diagnosis? Treatment?

Back 59

Present with either bilateral do unilateral retinal tumors. Individuals with bilateral often have other primary cancers.
Diagnosis: With retinoblastomas, a DNA test is done.
Treatment: Enucleation, radiation or chemotherapy, light therapy or cryotherapy.

Front 60

What type of gene is the RB gene?

Back 60

Tumor suppressor gene

Front 61

What are the genetics of sex reversal?

Back 61

Y-linked
Usually a somatic translocation and so rarely if ever gets passed on. The mutation often causes sterility.

Front 62

What genetic mutation occurs in sex reversal?

Back 62

The SRY gene usually fuses onto the X chromosome in males with XX.
There is often an SRY deletion in females with XY.

Front 63

What are the symptoms of sex reversal?

Back 63

Female (XY) ovaries do not develop as 2X's are required. Only mimic turner's if there is a large deletion of the Y gene.
Male (XX) sperm do not develop because you need more than the SRY gene. Similar to Kleinfelter's except for MR, behavior problems and these patients enter puberty spontaneously.

Front 64

Diagnosis for sex reversal? Treatment?

Back 64

When the phenotype doesn't match the karyotype, run FISH.
Treatment: For males, testosterone for under-virilization and surgical intervention for gynecomastia. For females, estrogen for puberty and removal of ovaries in adulthood to reduce risk of cancer.

Front 65

What is specific for sex reversal?

Back 65

Y-linked trait.

Front 66

What are the genetics of sickle cell anemia?

Back 66

Autosomal recessive with mutation in the B globin gene at the B6 position. Glutamine is replaced by a valine.

Front 67

Symptoms of sickle cell anemia?

Back 67

Anemia, failure to thrive, autolysis of spleen following splenomegaly, increased infections due to missing spleen.

Front 68

Treatments for sickle cell?

Back 68

Bone marrow transplant
Hydroxyurea

Front 69

What are the genetics of Tay-Sachs disease?

Back 69

Autosomal recessive is a mutation in the Hexosaminidase A enzyme which normally breaks down gangliosides. These accumulate and cause neuro-toxicity.

Front 70

Symptoms of Tay-Sachs? Diagnosis?

Back 70

Neurological deficits early in life with death by 2 years. Vision is lost within the first year with cherry red spots on fundoscopic exam.
Diagnosis: Test serum hexosaminidase A and newborn screening.

Front 71

What is specific about Tay-Sachs?

Back 71

It is common in Ashkenazic Jews and the Amish

Front 72

What are the genetics of Thalassemia?

Back 72

Autosomal recessive with mutation in α or β globin genes

Front 73

What are the symptoms of Thalassemia? Diagnosis? Treatment?

Back 73

Microcytic, hypochromic anemia, hemachromatosis and infections
Diagnosis: Hb electrophoresis
Treatment: Bone marrow transplant, folate supplements for RBC synthesis, treatment of infections, iron chelation and supply antioxidants.

Front 74

What is specific to α or β thal?

Back 74

α is more prevalent in Japanese people and β is more prevalent in greeks

Front 75

What are the genetics of thrombophilia?

Back 75

Autosomal dominant disorder where either factor V or protein C and S are mutated. Factor V leiden is not broken down by protein C in which case predisposes you to clotting. Less common is a mutation in protein C which prevents it from binding factor V.

Front 76

Symptoms of thrombophilia? Diagnosis? Treatment?

Back 76

Pulmonary emboli.
Diagnosis: Test serum factor V and serum protein C.
Treatment: Anticoagulation therapy

Front 77

What is specific to thrombophilia?

Back 77

Multifactorial disorder

Front 78

What are the genetics of Turner syndrome?

Back 78

Missing chromosome (XO), usually sporadic. 50% of the time XO, 25% 2nd X is deficient, 25% of the time patient is mosaic.

Front 79

What are the symptoms of Turner syndrome?

Back 79

Ovaries require 2X's to mature so in this case they scar and atrophy.
Main symptoms: Short stature, webbed neck, cystic hygroma, cardiac and renal abnormalities. Reduced estrogen predisposes them to atherosclerosis and heart disease.

Front 80

What is the treatment for Turner syndrome?

Back 80

GH to stimulate growth. Estrogen for female characteristics, progesterone for first period and echocardiogram to monitor heart problems.

Front 81

Diagnosis
Patient has rocker bottom feet, transposition of the great vessels, clenched fists, cleft lip and palate, petite facies and ear malformations
What is the cause?

Back 81

Trisomy 18
Non-disjunction of chromosome 18

Front 82

Diagnosis
Holoprosencephaly, polydactyly, congenital heart disease and cutis aplasia of the occiput
What is the cause?

Back 82

Trisomy 13
Non-disjunction of chromosome 13

Front 83

Patient has hypotonia, protruding tongues, small ears, medial epicanthal folds, MR, single palmar crease and brushfield spots
What is the disease and what caused it?

Back 83

Trisomy 21
Non-disjunction of chromosome 21 or Robertsonian translocation

Front 84

A child has ocular hypertelorism, MR, microcephaly and the cry sounds like a cat.
What is it and what caused it?

Back 84

Cri du chat
Deletion of the p arm of chromosome 5

Front 85

Child has thymic aplasia, hypocalcemia, tetralogy of fallot and MR.
What is it and what caused it?

Back 85

DiGeorge syndrome
Due to failure of neural crest cells to migrate. Deletion is on chromosome 22q11

Front 86

Male has under-virilization of the genitalia, tall stature, atrophied testes, MR and behavior problems.
Diagnosis? What caused it?

Back 86

Variant kleinfelter's syndrome due to behavior problems.
Numerous additional X chromosomes and a Y.

Front 87

Patient has cardiac defects, cleft palate, hyperextensible fingers and abnormal facial characteristics.
Diagnosis?

Back 87

Velocardiofacial syndrome (less severe than DiGeorge syndrome.

Front 88

Patient has paroxysms of laughter, seizures, abnormal EEG, severe MR, jerky movements and ataxia
Diagnosis? What type of inheritance is it? What caused it?

Back 88

Angelmann syndrome
Autosomal dominant
Deletion of maternal chromosome 15q12 or paternal (uniparental) disomy

Front 89

Patient has black spots in sclera and joints. Urine turns black upon standing
Diagnosis? What caused it?

Back 89

Alkaptonuria
Lack of homogentisic oxidase needed for breakdown of tyrosine. Increased homogentisic acid in the urine.

Front 90

Patient has mental retardation, seizures, small head, blond hair and blues eyes and smells musty.
Diagnosis? What caused it? Treatment?

Back 90

Phenylketonuria. Autosomal recessive disorder.
Lack of the enzyme phe hydroxlase or BH4 in malignant PKU.
Restrict phenyalanine in diet by restricting protein.

Front 91

Patient has neonatal jaundice, liver disease, cataracts and susceptibility to Ecoli infections.
Diagnosis? How would you confirm? Treatment?

Back 91

Galatosemia (GALT)
Reducing substance in the urine, serum levels of galactose-1-P uridyltransferase
Treatment: Soy based formula as soon as possible.

Front 92

Patient has failure to thrive, lethargy, constipation, low body temp and large anterior fontanelle.
Diagnosis? Inheritance pattern?

Back 92

Congenital hypothyroidism
95% sporadic

Front 93

Patient has vomiting, lethargy and encephalopathy following a fast. There is hypoglycemia and absence of ketone bodies in the urine.
Diagnosis? Inheritance? Which enzyme is absent? Treatment?

Back 93

MCADD
Autosomal recessive
Acyl-CoA dehydrogenase preventing ketone formation from medium chain fatty acids.
IV glucose and prevent fasting.

Front 94

What causes Burkitt's Lymphoma?

Back 94

A translocation between the c-myc proto-oncogene and the IgH gene. This involves chromosome 8 and 14.
It is autosomal dominant inheritance.

Front 95

Patient has parathyroid, pancreatic cell and anterior pituitary tumor. Diagnosis?

Back 95

MEN1 syndrome

Front 96

Patient has parathyroid tumor, medullary thyroid cancer and pheochromocytoma. Diagnosis? What caused it?

Back 96

MEN2 syndrome
A mutation in the RET oncogene. YOU ONLY NEED 1 MUTATION HERE.
Inheritance is autosomal dominant.

Front 97

Patient has brittle bones, wormian bones, short stature, hearing loss and dentinogenesis imperfecta. Diagnosis? Deficiency? Treatment?

Back 97

Osteogenesis imperfecta
The deficiency is type I collagen
Reduce contact sports, repair broken bones and weight bearing exercises.
Alendronate - bisphosphonates which inhibit osteoclast activity.

Front 98

Fetus characterized with molar placenta and syndactyly. Diagnosis?

Back 98

Triploidy (3 sets of all chromosomes).