Carrier screening Flashcards
What diseases should Ashkenazi Jewish people be screened for in a prenatal setting?
- Familial Dysautonomia
- Fanconi Anemia group c
- Tay Sachs
- Canavan Disease
- Neimann Pick type A
- Bloom Syndrome
- Mucolipidosis IV
- Gaucher Disease type 1
Carrier frequency for Cystic Fibrosis in the Caucasian population
1 in 25
Who should be screened for sickle cell?
African American population. 1 in 10 are carriers for S trait.
The disease encompasses a group of disorders characterized by the inheritance of at least one hemoglobin S trait.
HbSS- sickle cell anemia, caused by 2 copies of the s trait
HbSC- Also known as beta thalassemia, caused by compound heterozygous inheritance of both hemoglobin s trait and hemoglobin c trait.
Hemoglobin electrophoresis or genetic testing can diagnose these individuals.
Beta Thalassemia
Common in Mediterranean and middle eastern populations, carrier frequency is difficult to establish.
- Beta +: reduced beta-globin production
- Beta 0: absence of beta-globin production
Alpha Thalassemia
Only HbBart and HbH are clinically significant.
HbBart: deletion/dysfunction of all 4 alpha globin alleles, no residual function
HbH: Deletion/dysfunction of 3 alpha globin alleles, little residual function
Carriers of the alpha thalassemia trait can be:
Alpha 0-: Deletion/dysfunction of 2 alpha globin alleles, often in cis (–/++)
Alpha +: deletion/dysfunction of 1 alpha globin allele
Peripheral blood smear or hemoglobin studies can be performed for identification of carriers or affected individuals in addition to genetic studies.
Steps for carrier screening
Preconception: the mother should be screened first, screening should be based on her ethnicity. counsyl offers panels which cover a large majority of autosomal recessive diseases. Father should be tested after mothers results are received, if she is a carrier he can be screened for those particular diseases/mutations.
Prenatal screening works the same way.
Spinal Muscular Atrophy (SMA)
Severe neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, which results in proximal muscle weakness and paralysis
What is the second most common fatal autosomal recessive condition after cystic fibrosis?
Spinal Muscular Atrophy (SMA); prevalence 1 in 10,000 live births and a carrier frequency of 1/40 - 1/60
Spinal Muscular Atrophy (SMA) type 1 (Werdnig-Hoffman)
characterized by severe, generalized muscle weakness and hypotonia at birth or within the first 3 months of life. Death from respiratory failure usually occurs within the first 2 years.
SMA type II
Children are able to sit, although they cannot stand or walk unaided and survive beyond 4 years.
Type III SMA (Kugelberg-Welander)
Milder form, with onset during infancy or youth: patients learn to walk unaided
Primary SMA determining gene
- Survival Motor Neuron gene (SMN)
- SMN1: on 5q13 exon 7 (homozygously absent in approximately 95% of affected patients, with few exceptions)
- SMN2
Limitations of a SMA carrier test
- Approximately 2% of SMA cases arise as the result of de novo mutation events (high compared to most autosomal recessive disease)
- The copy number of SMN1 can vary on a chromosome; we have observed that approximately 5% of the normal population possess three copies of SMN1. It is therefore possible for a carrier to possess one chromosome with two copies and a second chromosome with zero copies. (RISK ASSESSMENT CALCULATIONS USING BAYES ARE ESSENTIAL FOR THE PROPER GENETIC COUNSELING OF SMA FAMILIES)
Who is being offered SMA carrier testing?
Individuals with a family history. However, ACMG recommends that since SMA is present in all populations, carrier testing should be offered to all couples.
