Chromosome Breakage Disorders Flashcards
- Chromosome translocation most commonly found in condition
- elevated AFP
- progressive cerebellar ataxia beginning between ages one and four years
- oculomotor apraxia
- choreoathetosis
- telangiectasias of the conjunctivae
- immunodeficiency
- increased risk for malignancy, particularly leukemia and lymphoma
- Ataxia-Telangiectasia
- ATM
- 11q22.3
A 7;14 chromosome translocation is identified in 5%-15% of cells in routine chromosome studies of peripheral blood of individuals with A-T. The break points are commonly at 14q11 (the T-cell receptor-alpha locus) and at 14q32 (the B- cell immunoglobulin heavy chain receptor [IGH] locus).
- 50% of individials with the diagnosis of ataxia-telangiectasia with lymphopenia screen positive for what condition on newborn screening
- SCID
For severe combined immunodeficiency identifies reduced T-cell receptor excision circle (TREC) levels. This method of NBS most likely identifies the estimated 50% of children with A-T who have lymphopenia
- Common clinical findings found in individuals with condition shown in picture
- Bloom syndrome
- BLM
- 15q26.1
- Post -natal growth deficiency
- increase risk of cancer (colon most common)
- insulin resistance (DM)
- Normal intelligence
- increase number of sister chromatid exchange
- early menopause
- infertility in males (azoospemia)
Heterozygous pathogenic variant in this gene known to cause AD Fanconi Anaemia
RAD51
hemizygous pathogenic variant in this gene known to cause X-linked fanconi anaemia.
FANCB
An individual with the following features are at increase risk for what malignancy?:
- short stature
- abnormal skin pigmentation
- skeletal abnormalities (pre-axial polydactyly)
- microcephaly
- progressive bone marrow failure with pancytopenia
Fanconi Anaemia
The incidence of acute myeloid leukemia is 13% by age 50 years.
BRCA2. Biallelic pathogenic variants in BRCA2 are associated with early-onset acute leukemia and solid tumors [Hirsch et al 2004, Wagner et al 2004, Myers et al 2012]. The cumulative probability of any malignancy was 97% by age six years, including AML, medulloblastoma, and Wilms tumor
PALB2. Solid tumors (e.g., medulloblastoma, Wilms tumor) are associated with PALB2 pathogenic variants [Reid et al 2007].
Medications used to treat the following in Fanconi Anaemia
- improve red cell and platelet counts
- neutrophil count
- known cure
- oral androgens
- G-CSF
- HSCT (hematopoetic stem cell transplant)
what is the underlying disease mechanism for Fanconi anaemia
- >5 of the FA proteins are assembled in a nuclear complex.
In response to
DNA damage, this complex activates monoubiquitination of FANCD2 and FANCI protein with
subsequent FA proteins involved in direct DNA repair
severe pre and post natal growth deficiency
immune abnormalities
sensitivity to light (sun senitive rash;butterfly distribution)
insulin resistance
women with early menopause and males areinfertile
cancer of a wide variety of types and anatomical sites
Bloom Syndrome
- BLM*
- Autosomal recessive*
increase frequency of sister chromatid exchange
