Hidden carriership of spinal muscular atrophy – implication for genetic canceling

Spinal muscular dystrophy (SMA) is a genetically determined neurodegenerative disease that, as a result of the loss of the motor neurons in the spinal cord, leads to muscle denervation, and then to their progressive weakness and atrophy. The disease is inherited in an autosomal recessive manner, caused by both parallelic mutations of the SMN1 gene located on chromosome 5. In 96% of patients, exon 7 homodeletion of the SMN1 gene is detected, while the remaining deletions within one allele are accompanied by a point mutation in the other. SMA carrier tests are based on determining the number of copies of the SMN1 gene – detection of one copy of this gene is interpreted as an unambiguous finding of a carrier status, detection of two or more copies of the SMN1 gene is interpreted as an exclusion of SMA carrier. Unfortunately, the frequent phenomenon of SMN1 and SMN2 gene conversion (difficult to identify directly) changes their number within the same chromosome. In family studies of inheritance of SMA carrier among 97 families, we detected 7 cases of hidden carrier consist in the presence of two copies of the SMN1 gene on one chromosome 5 with the simultaneous lack of this gene on the other chromosome 5. In addition, we detected 3 cases that are either cases of hidden carrier or newly formed mutations. It is known that in Poland at least one in 40 people has a mutation in its genome responsible for spinal muscular atrophy. The result of a carrier test in which it is excluded (based on the presence of two copies of the SMN1 gene) requires special care. The resolution can be brought by in-depth pedigree analysis and molecular research.