Congenital myopathies are heterogeneous group of neuromuscular disorders and characterised by hypotonia early onset muscular weakness, developmental delay. Congenital myopathies are classified into centranuclear myopathies, nemaline myopathies, core myopathies and congenital fiber-type disproportion based on major pathological features found in muscle biopsies.
Material and Methods
The present study was conducted on 25 syndromic orofacial cleft patients present with different clinical features. After clinical evaluation, genomic DNA was extracted by standard protocol (Qiagen kit). Clinical exome sequencing (illumina platform) was performed in patient DNA sample and sequencing data was analysed for sequence variant and identified variant validation was done by Sanger sequencing method.
A homozygous nonsense variant in exon 1 of the KLHL40 gene (chr3:42727712G>A: Depth 53×) that results in a stop codon and premature truncation of the protein at codon 201 (p.Trp201Ter; ENST000003297777) was detected.
This study suggest the involvement of KLHL40 mutation with fetal akinesia and severe namaline myopathies, also associated with cleft palate. At present scenario there is no evidence which recognize that cleft palate associated with severe nemaline myopathies and fetal akinesia.
Key Words: Congenital myopathy, Nemaline myopathy, KLHL40, Clinical Exome Sequencing.
Audience Take Away:
- Based on this study clinician will be able to produce proper management and therapy to patient
- Attendees will be able to provide proper diagnosis to patients with severe nemaline myopathy and fetal akinesia and cleft palate