Spinal Muscular Atrophy Due to Double Gene Conversion Event

ABSTRACT

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord. The survival motor neuron (SMN) gene has been identified as an SMA-determining gene. SMN exists as two copies in 5q13, and deletions in exons 7 and 8 of the telomeric copy (SMN^T) occur in 95% of patients, regardless of disease severity. In a minority of patients, exon 7 but not exon 8 of SMN^T appears deleted. We now report a patient with typical features of SMA type II who carried homozygous deletions of SMN^T exon 7 and centromeric SMN (SMN^C) exon 8 but retained SMN^T exon 8 and SMN^C exon 7. Sequence analysis demonstrated that SMN^C exon 7 was adjacent to SMN^T exon 8 on both SMN copies, indicating a double conversion. We confirm that sequence conversion is a common event in SMA and is associated with the milder form of the disease. The severity, however, can be modified in either positive or negative direction by other factors.

KEYWORDS: :

• copy number
• gene conversion
• MLPA
• SMA
• SMN^C
• SMN^T