RESUMO
Urinary incontinence (UI) is a common health condition that may interfere with the quality of life. A comprehensive evaluation of female UI helps with effective and safe treatments. Ultrasound has gained popularity to explore UI recently because it can collect crucial information for treatment planning and counseling. Translabial and introital approaches are commonly and reliably applied to ultrasound. The images can be obtained using two-dimensional and three-dimensional ultrasounds. Ultrasound is the only modality capable of confirming the presence or absence of a mid-urethral sling (MUS) and is able to demonstrate bulking agents as well. Although some of the ultrasound findings may only be incidental or supplementary to the patient's symptoms, ultrasound benefits for investigating the pathophysiology of UI and surgical outcomes of MUS procedures. It is anticipated that standardization in terminology, measurement techniques, and reporting can be established in the near future.
RESUMO
Accurate genetic diagnosis is necessary for guiding the treatment of spinal muscular atrophy (SMA). An updated consensus for the diagnosis and management of SMA was published in 2018. However, clinicians should remain alert to some pitfalls of genetic testing that can occur when following a routine diagnosis. In this study, we report the diagnosis of three unrelated individuals who were initially misdiagnosed as carrying a homozygous deletion of SMN1 exon 7. MLPA (P060 and P021) and qPCR were used to detect the copy number of SMN. SMN1 variants were identified by SMN1 clone and next-generation sequencing (NGS). Transcription of SMN1 variants was detected using qRT-PCR and ex vivo splicing analysis. Among the three individuals, one was identified as a patient with SMA carrying a heterozygous deletion and a pathogenic variant (c.835-17_835-14delCTTT) of SMN1, one was a healthy carrier only carrying a heterozygous deletion of SMN1 exon 7, and the third was a patient with nemaline myopathy 2 carrying a heterozygous deletion of SMN1 exon 7. The misdiagnosis of these individuals was attributed to the presence of the c.835-17_835-14delCTTT or c.835-17C > G variants in SMN1 intron 6, which affect the amplification of SMN1 exon 7 during MLPA-P060 and qPCR testing. However, MLPA-P021 and NGS analyses were unaffected by these variants. These results support that additional detection methods should be employed in cases where the SMN1 copy number is ambiguous to minimize the misdiagnosis of SMA.
RESUMO
BACKGROUND: We aimed to develop a high-fidelity long-read sequencing (LRS)-based approach to detect SMN gene variants in one step. It is challenging for conventional step-wise methods to simultaneously detect all kinds of variations between homologous SMN1 and SMN2. METHODS: In this study, LRS was developed to analyze copy numbers (CNs), full sequences, and structure of SMN1 and SMN2. The results were compared with those from the step-wise methods in 202 samples from 67 families. RESULTS: LRS achieved 100% (202/202) and 99.5% (201/202) accuracy for SMN1 and SMN2 CNs, respectively. It corrected SMN1 CNs from MLPA, which was caused by SNVs/indels that located in probe-binding region. LRS identified 23 SNVs/indels distributing throughout SMN1, including c.22dup and c.884A > T in trans-configuration, and a de novo variant c.41_42delinsC for the first time. LRS also identified a SMN2 variant c.346A > G. Moreover, it successfully determined Alu-mediated 8978-bp deletion encompassing exon 2a-5 and 1415-bp deletion disrupting exon 1, and the exact breakpoints of large deletions. Through haplotype-based pedigree trio analysis, LRS identified SMN1 2 + 0 carriers, and determined the distribution of SMN1 and SMN2 on two chromosomes. CONCLUSIONS: LRS represents a more comprehensive and accurate diagnosis approach that is beneficial to early treatment and effective management of SMA.