%0 Journal Article
%T Diagnosis of Challenging Spinal Muscular Atrophy Cases with Long-Read Sequencing.
%A Wang N
%A Jiao K
%A He J
%A Zhu B
%A Cheng N
%A Sun J
%A Chen L
%A Chen W
%A Gong L
%A Qiao K
%A Xi J
%A Wu Q
%A Zhao C
%A Zhu W
%J J Mol Diagn
%V 26
%N 5
%D 2024 May 13
%M 38490302
%F 5.341
%R 10.1016/j.jmoldx.2024.02.004
%X Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder primarily caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene. This study assesses the diagnostic potential of long-read sequencing (LRS) in three patients with SMA. For Patient 1, who has a heterozygous SMN1 deletion, LRS unveiled a missense mutation in SMN1 exon 5. In Patient 2, an Alu/Alu-mediated rearrangement covering the SMN1 promoter and exon 1 was identified through a blend of multiplex ligation-dependent probe amplification, LRS, and PCR across the breakpoint. The third patient, born to a consanguineous family, bore four copies of hybrid SMN genes. LRS determined the genomic structures, indicating two distinct hybrids of SMN2 exon 7 and SMN1 exon 8. However, a discrepancy was found between the SMN1/SMN2 ratio interpretations by LRS (0:2) and multiplex ligation-dependent probe amplification (0:4), which suggested a limitation of LRS in SMA diagnosis. In conclusion, this newly adapted long PCR-based third-generation sequencing introduces an additional avenue for SMA diagnosis.