What is the clinical evidence from this study?

Study design: Observational. Population: Congenital muscular dystrophy (n=48). Intervention: Target capture/next-generation sequencing. Primary outcome: Identification of CMD subtypes and causative genetic mutations.

What question did this study set out to answer?

To evaluate the phenotypic spectrum and underlying genetic variants in Taiwanese patients with suspected congenital muscular dystrophy using pathology-guided molecular analyses.

February 9, 2017PLoS ONEOpen Access

Comprehensive target capture/next-generation sequencing as a second-tier diagnostic approach for congenital muscular dystrophy in Taiwan

View Full Paper

Ask AI

Bookmark

Key result

Comprehensive target capture/next-generation sequencing successfully identified causative mutations in 14 of 15 patients with collagen VI deficiency and all 6 patients with merosin deficiency.

Population

48 Taiwanese patients suspected to have congenital muscular dystrophy screened by histochemistry and…

Design

Cohort

Authors

WLWen‐Chen LiangKaohsiung Medical University TXTian XiaNaval Medical Research Command CYChung‐Yee YuoKaohsiung Medical University

Discussion

Member takes

Implication

Supports targeted NGS panels for CMD diagnostics; leaves open need for larger prospective validation across populations.

Key Points

To evaluate the phenotypic spectrum and underlying genetic variants in Taiwanese patients with suspected congenital muscular dystrophy using pathology-guided molecular analyses.
Screened 48 patients in Taiwan with suspected congenital muscular dystrophy using muscle histochemistry and immunohistochemistry to categorize subtypes.
Selected diagnostic genetic testing modalities, including direct sequencing and next-generation sequencing panels, according to initial histopathological and clinical classifications.
Identified causative COL6A1, COL6A2, or COL6A3 mutations in 14 of 15 patients with sarcolemma-specific collagen VI deficiency, who presented with distal hyperlaxity and milder disease severity than typically reported.
Confirmed LAMA2 mutations in all six patients with merosin deficiency, with clinical manifestations demonstrating a higher proportion of intellectual disability and epilepsy.
Detected causative variants in POMT1, TRAPPC11, and LMNA among remaining patients categorized by alpha-dystroglycan reduction or inflammatory changes on muscle biopsy.

Study Design

Type

Observational (n=48)

Multicenter

Structured PICO

Population

48 Taiwanese patients with suspected congenital muscular dystrophy, characterized by early-onset hypotonia and muscle weakness, who underwent histopathological and genetic evaluation.

Exposure

Target capture/next-generation sequencing (NGS) as a second-tier diagnostic approach.

Outcome

Identification of causative genetic mutations and establishment of genotype-phenotype correlations.

Target capture/next-generation sequencing is an effective second-tier diagnostic tool for congenital muscular dystrophy, revealing that Ullrich type CMD is the most common form in this Taiwanese cohort.

Limitations

Potential selection bias as some floppy babies with congenital brain/eye anomalies might not be recognized as CMD or referred for muscle biopsy.
Difficulty in arranging muscle MRI in Taiwan due to availability and cost.
Small sample sizes for certain CMD subtypes.

Cite This Study

Liang et al. (2017) conducted an observational in Congenital muscular dystrophy (n=48). Target capture/next-generation sequencing was evaluated on Identification of CMD subtypes and causative genetic mutations. Comprehensive target capture/next-generation sequencing successfully identified causative mutations in 14 of 15 patients with collagen VI deficiency and all 6 patients with merosin deficiency.

synapsesocial.com/papers/6a92ed88cfcd15eebf771fbc https://doi.org/10.1371/journal.pone.0170517

View Full Paper

Ask AI

Bookmark