Breakage Syndromes Flashcards
Number of complementation groups seen in FA
15 on OMIM
% FA that is mosaic
10-25%
Incidence of Bloom syndrome
1/160,000 uk but A.jews is 1/50,000
Phenotype of Bloom syndrome
Male infertile, female sub fertile , face, hypo/hyper skin pigmentation, iugr/gr, increased malignancy risk - leukaemia by 22 and solid tumours by 35. Immunodeficiency
Gene implicated in Bloom syndrome and location
BLM 15q26.1. DNA helicase
How analyse Bloom syndrome referral
Add 0.1 ml BrDU before incubation, cultures are light sensitive, Measure spontaneous sce freq using harlequin stain. normal 6-10/ cell. Blooms >50
What is ataxia telangiectasia
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.
Phenotype of ataxia telangiectasia
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
Gene involved in A-T
ATM 11q22.3
Cyto abnormalities seen in A-T
T(7;14) in 5-15% but is not diagnostic
Incidence of Nijmegen breakage syndrome
1/100,000 increased in Slavic pop
Nijmegen BS phenotype
Short, bird like face, GR, DD, MR, immunodeficiency , inc malignancy risk - NHL by 15years, decreased t-cells
Gene and locus in Nijmegen bs
NBN at 8q21 encodes Nibrin which regulates cell division
Cyto abnormalities seen in Nijmegen bs
Immuno rearrangements- TCR and IgH genes, aneuploidy, markers, increased breaks, telomere fusions, cyto not used in diagnosis
Phenotype of Roberts syndrome
Iugr, severe limb abnormalities, craniofacial abn-cleft
Gene and locus in Roberts syndrome
ESCO2 8p21.1. Protein involved in establishing sister chromatid adhesion in s phase
Cyto abnormalities seen in Roberts syndrome
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
Phenotype of X-P
Dry skin, v sensitive to uV- affects skin eyes and CNS, inc cancer risk, 30% neuro probs, changes in skin pigmentation
Genetics of X-P
At least 8 inherited forms. >50% mutations in POLH, XPC, ERCC2
Cyto abn in X-p
UV -> increased sce and chromatic abberations
Incidence of X-P
1/450,000 n Europe. Increased in Japan, n Africa, m east- 1/50,000
Cyto abnormalities in ICF syndrome
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
What is ICF
Immunodeficiency, centromere can instability, facial anomalies. Respiratiry infections
Gene involved in ICF
DNMT3B on 20q
Describe MVA
Mosaic variegated aneuploidy. Rare. Iugr/GR, inc malignancy risk, microcephaly, mosaic aneuoloidies with all chromosomes represented and see PCS. BUB1B gene 15q15.1. AR
Phenotype of FA
Increased risk malignancy- all lineages, skeletal abns, iugr, microcephaly, average death by 16 years
how is FA analysed cytogenetically
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
