Genetic Counseling

SMA Genetic Risk Assessment

Methods of SMA genetic risk assessment for various clinical settings have been described in great depth.[3,10] Risk assessment is an integral part of genetic testing. The purpose of genetic risk assessment is to provide family members with risk estimates as accurately as possible for their decision making. Risk assessment for SMA is particularly important, because of the complexity of SMA genetics. The disease allele frequency is relatively high; small intragenic mutations are undetectable by the standard assays; the paternal de novo mutation rate is high; and the presence of two copies of SMN1 on one chromosome 5 can mask a deletion/conversion mutation on the other chromosome 5 in SMN gene dosage analyses.

It should be noted that genetic risk assessments are estimates based on published data from a finite number of cases in specific populations. It should also be noted that additional family information, especially additional genetic information, often dramatically improves the accuracy of genetic risk assessments. Thus genetic risk assessment is often an ongoing process, and genetic testing on additional family members should be performed whenever indicated by the initial results.[10]

SMN1 Allele and Genotype Frequencies

For SMA risk assessment, normal and disease allele frequencies have been estimated.[10] Most disease alleles in SMA are deletions (or conversions) of at least exon 7 of SMN1 (''0-copy'' alleles). A normal chromosome 5 usually has one copy of SMN1 (''1-copy'' allele). However, two copies of SMN1 are often present on the same chromosome 5, for which we use the term ''2-copy allele.'' We refer to disease alleles with small, intragenic mutations in SMN1 as

-copy-disease'') alleles. Updated frequency of each SMN1 allele or genotype is listed in Table 1 (modified from Ref. [11]).

Table 1 Updated SMN1 allele and genotype frequencies




9.88 x 10" 9.50 x 10" 4.04 x 10" 1.81 x 10"

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

Get My Free Ebook

Post a comment