Whole Exome Sequencing Reveals a BSCL2 Mutation Causing Progressive Encephalopathy with Lipodystrophy (PELD) in an Iranian Pediatric Patient

Iran Biomed J. 2016 Nov;20(5):295-301. doi: 10.22045/ibj.2016.07. Epub 2016 Jul 25.

Abstract

Background: Progressive encephalopathy with or without lipodystrophy is a rare autosomal recessive childhood-onset seipin-associated neurodegenerative syndrome, leading to developmental regression of motor and cognitive skills. In this study, we introduce a patient with developmental regression and autism. The causative mutation was found by exome sequencing.

Methods: The proband showed a generalized hypertonia and regression of all developmental milestones. Based on the advantages of next-generation sequencing (NGS), whole exome sequencing (WES) was requested. The functional significance of variants was evaluated by NGS-specific prediction servers. Sanger sequencing was used for segregation analysis in the family.

Results: There was no specific sign in the clinical and paraclinical investigations of the patient to establish a conclusive clinical diagnosis. WES detected a known homozygous nonsense mutation in BSCL2 (NM_001122955.3:c. 985C>T; p.Arg329*). The variant is segregating in the pedigree with an autosomal recessive pattern.

Conclusion: Exome sequencing is a robust method for identifying the candidate gene variants in Mendelian traits.

Keywords: BSCL2; Exome; Iran; Seipin.

Publication types

  • Case Reports

MeSH terms

  • Autistic Disorder / genetics*
  • Base Sequence
  • Brain Diseases / genetics*
  • Child
  • DNA Mutational Analysis
  • Developmental Disabilities / genetics*
  • Exome / genetics
  • GTP-Binding Protein gamma Subunits / genetics*
  • Genetic Predisposition to Disease / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lipodystrophy / genetics*
  • Male
  • Mutation / genetics
  • Pedigree
  • Sequence Analysis, DNA

Substances

  • BSCL2 protein, human
  • GTP-Binding Protein gamma Subunits