Breakage Syndromes

Question 1

Number of complementation groups seen in FA

Answer 1

15 on OMIM

Question 2

% FA that is mosaic

Answer 2

10-25%

Question 3

Incidence of Bloom syndrome

Answer 3

1/160,000 uk but A.jews is 1/50,000

Question 4

Phenotype of Bloom syndrome

Answer 4

Male infertile, female sub fertile , face, hypo/hyper skin pigmentation, iugr/gr, increased malignancy risk - leukaemia by 22 and solid tumours by 35. Immunodeficiency

Question 5

Gene implicated in Bloom syndrome and location

Answer 5

BLM 15q26.1. DNA helicase

Question 6

How analyse Bloom syndrome referral

Answer 6

Add 0.1 ml BrDU before incubation, cultures are light sensitive, Measure spontaneous sce freq using harlequin stain. normal 6-10/ cell. Blooms >50

Question 7

What is ataxia telangiectasia

Answer 7

Ataxia telangiectasia (A-T) (also referred to as Louis–Bar syndrome ) is a rare, neurodegenerative, Autosomal recessive, inherited disease causing severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease.

Question 8

Phenotype of ataxia telangiectasia

Answer 8

Prog cerebellar ataxia, truncal ataxia, jerky movements, slur, no walk, ocular telangiectasia- red by 5 years, inc AFP in blood, inc. malignancy risk (all and lymphoma) (35%), 50% die by 25- pulmonary failure, susceptible to X-Ray

Question 9

Gene involved in A-T

Answer 9

ATM 11q22.3

Question 10

Cyto abnormalities seen in A-T

Answer 10

T(7;14) in 5-15% but is not diagnostic

Question 11

Incidence of Nijmegen breakage syndrome

Answer 11

1/100,000 increased in Slavic pop

Question 12

Nijmegen BS phenotype

Answer 12

Short, bird like face, GR, DD, MR, immunodeficiency , inc malignancy risk - NHL by 15years, decreased t-cells

Question 13

Gene and locus in Nijmegen bs

Answer 13

NBN at 8q21 encodes Nibrin which regulates cell division

Question 14

Cyto abnormalities seen in Nijmegen bs

Answer 14

Immuno rearrangements- TCR and IgH genes, aneuploidy, markers, increased breaks, telomere fusions, cyto not used in diagnosis

Question 15

Phenotype of Roberts syndrome

Answer 15

Iugr, severe limb abnormalities, craniofacial abn-cleft

Question 16

Gene and locus in Roberts syndrome

Answer 16

ESCO2 8p21.1. Protein involved in establishing sister chromatid adhesion in s phase

Question 17

Cyto abnormalities seen in Roberts syndrome

Answer 17

80% show PCS. Puffing of qh regions due to heterochromatin repulsion, aneuoloidies, micronucleation, cells slow growing as Chrs don’t line up at cen well. ‘Railroad track’ chrs

Question 18

Phenotype of X-P

Answer 18

Dry skin, v sensitive to uV- affects skin eyes and CNS, inc cancer risk, 30% neuro probs, changes in skin pigmentation

Question 19

Genetics of X-P

Answer 19

At least 8 inherited forms. >50% mutations in POLH, XPC, ERCC2

Question 20

Cyto abn in X-p

Answer 20

UV -> increased sce and chromatic abberations

Question 21

Incidence of X-P

Answer 21

1/450,000 n Europe. Increased in Japan, n Africa, m east- 1/50,000

Question 22

Cyto abnormalities in ICF syndrome

Answer 22

Windmill multi radials of 1,9,16 caused by interchange between her regions after PHA stimulation. instability of pericentromeric regions caused by hypometh of satellite DNA, sce freq normal. Also see deletions or Rea of these regions

Question 23

What is ICF

Answer 23

Immunodeficiency, centromere can instability, facial anomalies. Respiratiry infections

Question 24

Gene involved in ICF

Answer 24

DNMT3B on 20q

Question 25

Describe MVA

Answer 25

Mosaic variegated aneuploidy. Rare. Iugr/GR, inc malignancy risk, microcephaly, mosaic aneuoloidies with all chromosomes represented and see PCS. BUB1B gene 15q15.1. AR

Question 26

Phenotype of FA

Answer 26

Increased risk malignancy- all lineages, skeletal abns, iugr, microcephaly, average death by 16 years

Question 27

how is FA analysed cytogenetically

Answer 27

Patients with Fanconi’s anaemia show increased levels ofspontaneous chromosome damage and hypersensitivity to the effects of alkylating agents such as mitomycin C (MMC) and diepoxybutane (DEB). This hypersensitivity manifests as high levels of chromosome
damage as compared to a control in cultures exposed to the alkylating agent