Clinical question and test results:
III1 is affected with SMA type I (OMIM
253300). Laboratory analysis by MLPA
indicates homozygous deletion for SMN1. The
mother (II2) is subsequently tested also and
found to have a single copy of SMN1 -
consistent with carrier status. Her sister
(II3) sees a clinical geneticist regarding
her carrier status. MLPA analysis is
performed by the lab which indicates two
copies of SMN1. It is most likely that she
is not a carrier, but what is the residual
risk?
Nobody else in the pedigree has been tested,
although they are known to be clinically
unaffected.
The complication for the risk calculation is
that approximately 4% (3.8% according to the
reference below) of 'normal'
chromosomes have two copies of SMN1, which
can mask a deletion on the other chromosome.
Assumptions:
Reference source for allele frequencies:
Ogino et al, Eu J Hum Genet, 2004, Dec 12
(12) 1015-23.
0 - copy disease allele = 0.013
1 - copy disease allele = 0.00024
1 - copy normal allele = 0.95
2 - copy normal allele = 0.038
Assume all alleles are at Hardy-Weinberg
equilibrium. |
