Evaluation of exonic copy numbers of SMN1 and SMN2 genes in SMA

• Published in: Gene 2022-05, Vol.823, p.146322-146322, Article 146322
• Main Authors: Arikan, Yunus, Berker Karauzum, Sibel, Uysal, Hilmi, Mihci, Ercan, Nur, Banu, Duman, Ozgur, Haspolat, Senay, Altiok Clark, Ozden, Toylu, Asli
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Carrier test; Child; Child, Preschool; Consanguinity; DNA Copy Number Variations; Exons; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; MLPA; Muscular Atrophy, Spinal - genetics; Mutation Rate; Sequence Deletion; SMA; SMN genes; Survival motor neuron; Survival of Motor Neuron 1 Protein - genetics; Survival of Motor Neuron 2 Protein - genetics; Young Adult
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2022.146322

•The clinical and genetic manifestations of SMA are diverse and heterogeneous.•In this paper, we report on the final mutation profiles of the SMN1 and SMN2 genes in terms of exonic deletions.•This is significant because the exact copy number of the SMN2 gene seems to be the determiner in our patients with SMA.•Furthermore, the chaotic manner of the SMN1 and SMN2 gene structures within their respective exonic regions resulted in different inheritance patterns in a family that was segregated in this study.•We also produced an “MLPA-SMA signature” which can be helpful in the initial preparation of patient reports. SMA is a neuromuscular disease and occurs primarily through autosomal recessive inheritance. Identification of deletions in the SMN1 gene especially in the exon 7 and exon 8 regions (hot spot), are used in carrier testing. The exact copy numbers of those exons in the SMN1 and SMN2 genes in 113 patients who presented with a pre-diagnosis of SMA were determined using MLPA method. We aimed to reveal both the most common copy number profiles of different SMA types. It was found that the frequency of homozygous deletions in SMN1 was 15.9%, while heterozygous deletions was 16.9%. The most common SMN-MLPA profile was 0–0-3–3. In the cases with homozygous deletion, SMA type III diagnosis was observed most frequently (44%), and the rate of consanguineous marriage was found 33%. Two cases with the same exonic copy number profile but with different clinical subtypes were identified in a family. We also detected distinct exonic deletion and duplication MLPA profiles for the first time. We created “the SMA signature” that can be added to patient reports. Furthermore, our data are important for revealing potential local profiles of SMA and describing the disease in genetic reports in a way that is clear and comprehensive.