Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FD9 > 130 - Hereditary Disorders of Genome Instability and DNA Repair > Flashcards

130 - Hereditary Disorders of Genome Instability and DNA Repair Flashcards

1
Q

Y/N: Although hereditary disorders of genome instability and DNA repair are rare, heterozygous carriers of affected genes, which may comprise several percent of the general population, may carry an increased cancer risk as well

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Spontaneous genome instability is present in

A

Bloom syndrome
Ataxia telangiectasia
Fanconi anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Genome instability is present in cells from patients with _____ only after exposure to DNA-damaging agents

A

Xeroderma pigmentosum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

The nucleotide excision repair (NER) pathway, which possesses bulky DNA lesions, including UV-induced DNA photoproducts, is impaired in _____. However, only XP patients have an increased cancer risk

A

Xeroderma pigmentosum
Cockayne syndrome
Trichothiodystrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Defects in the DNA mismatch repair result in

A

Hereditary nonpolyposis colon cancer (Lynch syndrome) and its subform, Muir-Torre syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

RecQ family members are mutated in

A

Bloom syndrome
Werner syndrome
Rothmund-Thomson syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Accelerated telomere shortening is a hallmark of cells from patients with the cancer-prone disorder

A

Dyskeratosis congenita

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Genome instability may result from a defect in BASC, a multienzyme complex centered around the BRCA1 protein in the nucleus, and cause the genome instability disorders including

A 
Ataxia-telangiectasia
Seckel syndrome
Nijmegen breakage syndrome
Hereditary breast cancer
Bloom syndrome
Fanconi anemia
Hereditary colon cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

CUTANEOUS
Photosensitivity (burning on sun exposure), poikiloderma, alopecia

NEOPLASIA
Osteosarcomas, cutaneous SCC, and others

OTHER
Skeletal abnormalities, growth deficiency, juvenile cataracts, osteoporosis

A

Rothmund-Thomson syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

CUTANEOUS
Cafe-au-lait macules
NEOPLASIA
Myeloid leukemia, SCC of the head and neck

OTHER
Aplastic anemia, pancytopenia growth retardation, thumb and other bone abnormalities

A

Fanconi anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

CUTANEOUS
Lacy, reticular pigmentation of neck and upper chest, nail dystrophy, premature gray hair, hyperhidrosis, skin cancer

NEOPLASIA
Mucosal leukoplakia leading to cancer of anus or mouth, Hodgkin disease, pancreatic adenocarcinoma

OTHER
Stenosis of lacrimal duct, anemia, pancytopenia, immunodeficiency, learning difficulties, deafness, brain calcifications, cerebellar hypoplasia, testicular atrophy, short stature, intrauterine growth retardation, retinopathy

A

Dyskeratosis congenita

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

CUTANEOUS
Telangiectasias

NEOPLASIA
T-cell leukemia, lymphomas

OTHER
Progressive cerebellar ataxia, immune defects, hypogonadism, increased acute toxicity of therapeutic X-ray

A

Ataxia-telangiectasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Similar to AT, but no ocular telangiectasias

A

AT-like disorder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CUTANEOUS
Cafe-au-lait macule, vitiligo

NEOPLASIA
B-cell and T-cell lymphomas, rhabdomyosarcoma, neuroblastoma

OTHER
Immune defects, growth retardation, microcephaly, mental retardation, characteristic facies

A

Nijmegen breakage syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

CUTANEOUS
Cafe-au-lait macules

NEOPLASIA
Leukemia

OTHER
Proportionate dwarfism, microcephaly, mental retardation, characteristic facies (receding forehead, narrow face, large beaked nose, micrognathia), immune deficiency, pancytopenia

A

Seckel syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

CUTANEOUS
Photosensitivity (burning on minimal sun exposure in some patients), freckle-like (lentiginous) macules, poikiloderma, skin cancer

NEOPLASIA
BCC, SCC, melanoma, CNS tumors

OTHER
Sensorineural deafness, progressive neurologic degeneration, primary loss of neurons

A

Xeroderma pigmentosum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Onset of freckling (lentigines) on sun-exposed skin in XP before age _____ in most patients

A

2 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Median age of onset of nonmelanoma skin cancer in XP

A

8 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

_____ abnormalities are almost as common as the cutaneous abnormalities and are an important feature of XP

A

Ocular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Y/N: posterior portion of the eye is affected in XP

A

No - The posterior portion of the eye (retina) is shielded from UV radiation by the anterior, UV-exposed structures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Most severe from of XP which involves the cutaneous and ocular manifestations of classic XP plus additional neurologic and somatic abnormalities, including microcephaly, progressive mental deterioration, low intelligence, hyporeflexia or areflexia, choreoathetosis, ataxia, spasticity, Achilles tendon shortening leading to quadriparesis, dwarfism, and immature sexual development

A

De Sanctis-Cacchione syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Predominant neuropathologic abnormality found at autopsy in XP patients with neurologic symptoms was

A

Loss (or absence) of neurons, particularly in the cerebrum and cerebellum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Median age of death of persons with XP with neurodegeneration

A

29 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Median age of death of persons with XP without neurodegeneration

A

37 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

XP DNA excision repair-deficient complementation groups

A

XPA-A to XPA-G

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Mutated genes identified in XP

A

DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XPC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Patients with clinical XP but normal NER

A

XP variants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

XP complementation group _____ contains patients with the most-severe neurologic and somatic abnormalities (the De Sanctis-Caccione syndrome), as well as patients with minimal or no neurologic abnormalities

A

A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Most common form of XP in Japan

A

XP complementation group A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

XP with skin and ocular involvement but without neurologic abnormalities
Typically do not give a history of blistering sunburns on minimal sun exposure and at times are first diagnosed with the appearance of skin cancer in a child

A

XP complementation group C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Most common group of XP in the United States, Europe and Egypt

A

C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

XP complementation group _____ patients are found mainly in Japan
Most have mild clinical symptoms without neurologic abnormalities or skin cancer

A

F

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

In XP variant, there is a defect in an error-prone, translesional DNA damage bypass polymerase, _____

A

POLH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Y/N: Both parents of XP patients are aysmptomatic carriers of mutations in of these genes

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

There is a _____ chance that their offspring will have inherited a mutated allele form each parent and thus have symptomatic XP

A

1 in 4

36
Q

DNA-damaging agents that have been found to yield hypersensitive responses with XP cells

A

Drugs (psoralens, chlorpromazine)
Cancer chemotherapeutic agents (cisplatin, carmustine)
Chemical carcinogens (benozopyrene derivatives present in cigarette smoke)

37
Q

Differential diagnosis of XP that is a disorder of amino acid absorption resulting from biallelic pathogenic variants in SLC6A19, a nonpolar amino acid transporter
Affected individuals may have reduced levels of niacin with resulting pellagra-like symptoms of photosensitivity with dermatitis, diarrhea, and dementia

A

Hartnup disorder

38
Q

Differential diagnosis of XP that is characterized by lentigines without evidence of the usually associated signs of skin damage, such as atrophy and telangiectasia (ie, poikiloderma), and cutaneous findings are not limited to sun-exposed sites

A

Carney complex

39
Q

CUTANEOUS
Photosensitivity (burning on minimal sun exposure in some patients)

NEOPLASIA
No increased incidence

OTHER
Typical facial features (deep-set eyes, loss of subcutaneous fat), pigmentary retinal degeneration, postnatal growth failure, sensorineural deafness, progressive neurologic degeneration, primary dysmyelination, brain calcifications

A

Cockayne syndrome

40
Q

Most common causes of death in XP

A

Skin cancer
Neurologic degeneration
Internal cancer

41
Q

Cells from CA patients have a defect in transcription coupled DNA repair with approximately two-thirds having mutations in the _____ gene and one-third with mutations in the _____ gene

A

CSB (ERCC6)

CSA (ERCC8)

42
Q 
Diagnostic criteria for CS:
Minor criteria (3 out of 5)
A 
Cutaneous photosensitivity
Pigmentary retinopathy and/or cataracts
Progressive sensorineural hearing loss
Tooth enamel hypoplasia
Bilateral calcifications of the putamen
43
Q

Diagnostic criteria for CS:

Brain imaging criteria

A

White matter hypomyelination
Cerebellar atrophy or hypoplasia
Bilateral calcifications of the putamen

44
Q 
Diagnostic criteria for CS:
Major criteria (mandatory)
A

Developmental delay
Progressive growth failure
Progressive microcephaly

45
Q

Median age of date in CS

A

8.4 years

46
Q

Single most important prognostic factor with a statistically significant association with reduced survival, earlier onset of hearing loss, and earlier onset of contractures in CS

A

Presence of cataracts before 3 years of age

47
Q

CUTANEOUS
Brittle hair, photosensitivity (burning on minimal sun exposure in some patients), ichthyosis, collodion membrane, “tiger tail banding” of hair with polarized microscopy

NEOPLASIA
No increased incidence

OTHER
Congenital cataracts, short stature, developmental delay, microcephaly, brain dysmyelination (failure to develop white matter), recurrent infections

A

Trichothiodystrophy

48
Q

Characterized by sulfur-deficient brittle hair

A

Trichothiodystrophy

49
Q

TTD is caused by different mutations in some of the same genes that cause _____

A

XP

50
Q

The functional defect in XP is abnormal repair, whereas the abnormality in TTD is thought to be related to

A

Transcription

51
Q

Majority of TTD patients have a defect in

A

XPD (ERCC2)

52
Q

Disease onset of Cockayne syndrome is usually in the _____ year of life

A

Second

53
Q

Most deaths in TTD are caused by

A

Infection

54
Q

_____ patients have an unusual combination of osteosclerosis of the axial skeleton and osteopenia of the peripheral skeleton

A

TTD

55
Q

CUTANEOUS
Sebaceous tumors (benign and malignant)
Keratoacanthomas

NEOPLASIA
Low-grade cancer of the colon, endometrium, stomach, small intestine, hepatobiliary system, upper urethral tract, larynx, and ovary; sebaceous carcinoma; BCC with sebaceous differentiation

A

Hereditary nonpolyposis colon cancer/Muir-Torre syndrome

56
Q

CUTANEOUS
Photosensitivty (burning on sun exposure), malar erythema, cafe-au-lait macules

NEOPLASIA
Most cancer types, particularly leukemias, lymphomas, carcinomas of the breast and GI tract

OTHER
Immune deficiency, growth retardation, unusual facies, male infertility and female subfertility, Type II diabets

A

Bloom syndrome

57
Q

BS is caused by a mutation in

A

BLM, a RecQ helicase

58
Q

BS is most frequent among

A

Ashkenazi Jews

59
Q

_____ cells are characterized by an increase in the frequency of spontaneous sister chromatid exchanges between homologous chromosomes
Characterized by hyperrecombination

A

BS

60
Q

BS patients usually die before the age of 30 years from

A

Either cancer or infection

61
Q

CUTANEOUS
Graying of hair, skin atrophy, leg ulcers, melanomas

NEOPLASIA
Sarcomas, thyroid cancer, meningiomas, melanomas (acral lentiginous and mucous membrane melanomas)

OTHER
Premature aging (atherosclerosis, diabetes mellitus, osteoporosis, cataracts)
A

Werner syndrome

62
Q

Rare disorder of premature aging (progeria) with an increased cancer risj

A

Werner syndrome (adult progeria)

63
Q

WS is caused by a mutation in

A

WRN, a RecQ helicase

64
Q

Cells in ______ demonstrate impaired DNA metabolism and a reduced replicative life span

A

WS

65
Q

Most WS patients are

A

Japanese

66
Q

Y/N: Patients with WS are clinically normal until adolescence

A

Yes

67
Q

Often, _____ are the first to make a diagnosis of WS as _____ develop early

A

Ophthalmologists

Cataracts

68
Q

10:1 ratio between epithelial and mesenchymal cancer seen in a normally aging population is shifted to _____ in WS patients

A

1:1

69
Q

Death from _____ usually occurs before the age of 50 years in WS

A

Myocardial infarction or cancer

70
Q

Rare chromosomal instability syndrome with an increased cancer risk and a typical poikiloderma that starts on the face during infancy

A

Rothmund-Thomson syndrome

71
Q

In two-thirds of patients, RTS is caused by a mutation in the DNA helicase

A

RecQL4

72
Q

RTS patients have a predisposition for cancer, in particular for

A

Osteosarcomas

73
Q

Y/N: Life expectancy is limited by cancer, but is normal in RTS without cancer

A

Yes

74
Q

FA is an autosomal recessive or in the case of _____ X-linked disease

A

Fanconi anemia complementation group B

75
Q

The estimated incidence of Fanconi anemia is higher in

A

Afrikaners and Ashkenazi Jews

76
Q

If patients with FA survive aplastic anemia and/or leukemia, they often develop solid tumors by the fifth decade of life, mostly

A

Squamous cell carcinomas of the head and neck and the anogenital areas

77
Q

FA is genetically heterogeneous with _____ complementation groups

A

19

78
Q

FA proteins have been shown to act in a common DNA damage recognition and repair pathway, which also involves

A

BRCA1 and BRCA2

79
Q

Increased chromosome breakage after exposure to DNA crosslinking agents such as mitomycin C or diepoxybutane is a feature of

A

FA

80
Q

Treatment of choice for aplastic anemia/myelodysplastic syndrome and leukemia

A

Allogenic hematopoietic stem cell transplantation

81
Q

Rare telomere instability syndrome with an increased risk for pancytopenia, myelodysplasia, and acute myeloid leukemia

A

Dyskeratosis congenita

82
Q

Dyskeratosis congenita patients commonly present with a triad of

A

Reticulated hyperpigmentation
Dystrophic nails
Mucosal leukoplakia

83
Q

Mode of inheritance of dyskeratosis congenita

A

X-linked

Also with autosomal dominant recessive forms

84
Q

Main cause of early death in dyskeratosis congenita

A

Bone marrow failure

85
Q

Short telomere length is a typical finding in _____ and used for diagnosis

A

Dyskeratosis congenita

FD9 (108 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions