Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features

BMC Med Genet. 2015 Jun 25;16:41. doi: 10.1186/s12881-015-0183-0.


Background: Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits.

Methods: Clinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations.

Results: We identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population.

Conclusion: We suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Autistic Disorder / genetics
  • Autistic Disorder / pathology*
  • Base Sequence
  • Developmental Disabilities / classification
  • Developmental Disabilities / ethnology
  • Developmental Disabilities / genetics
  • Developmental Disabilities / pathology
  • Female
  • Fingers / abnormalities*
  • Fingers / pathology
  • Genes, Recessive
  • Genotype
  • Haplotypes / genetics
  • Homozygote
  • Humans
  • Intellectual Disability / classification
  • Intellectual Disability / ethnology
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology*
  • Male
  • Microcephaly / classification
  • Microcephaly / ethnology
  • Microcephaly / genetics*
  • Microcephaly / pathology*
  • Molecular Sequence Data
  • Muscle Hypotonia / classification
  • Muscle Hypotonia / ethnology
  • Muscle Hypotonia / genetics*
  • Muscle Hypotonia / pathology*
  • Myopia / classification
  • Myopia / ethnology
  • Myopia / genetics*
  • Myopia / pathology*
  • Obesity / classification
  • Obesity / ethnology
  • Obesity / genetics*
  • Obesity / pathology*
  • Pakistan
  • Pedigree
  • Phenotype*
  • Retinal Degeneration
  • Sequence Analysis, DNA
  • Sequence Deletion / genetics*
  • Vesicular Transport Proteins / genetics*


  • VPS13B protein, human
  • Vesicular Transport Proteins

Supplementary concepts

  • Cohen syndrome