RIN2 and BBS7 variants as cause of a coincidental syndrome

Eur J Med Genet. 2020 Mar;63(3):103755. doi: 10.1016/j.ejmg.2019.103755. Epub 2019 Sep 12.

Abstract

BBS7 and RIN2 variants cause Bardet Biedl syndrome and RIN2 syndrome respectively. We investigated a consanguineous family in which five individuals manifested different phenotypes. Whole-exome sequencing analyses of the individual with multiple phenotypes revealed homozygosity for novel pathogenic variants in his DNA sample; a frameshift variant in RIN2 (c.1938delT) and a splice-site variant in BBS7 (c.1677-1G > A). Other affected individuals were homozygous for a variant in only one of either gene and consequently manifested phenotypes respective to one disorder. Our work shows that exome sequencing of the most severely affected individual can help in the identification of pathogenic variants in more than one involved genes in a particular family.

Keywords: Bardet-Biedl syndrome; Ciliopathy; MACS; Pakistan.

Publication types

  • Case Reports

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Alopecia / genetics*
  • Alopecia / physiopathology
  • Bardet-Biedl Syndrome / genetics*
  • Bardet-Biedl Syndrome / physiopathology
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Ciliopathies / genetics*
  • Cutis Laxa / genetics*
  • Cutis Laxa / physiopathology
  • Cytoskeletal Proteins / genetics*
  • Exome Sequencing
  • Female
  • Frameshift Mutation
  • Genotype
  • Guanine Nucleotide Exchange Factors / genetics*
  • Homozygote
  • Humans
  • Male
  • Megalencephaly / genetics*
  • Megalencephaly / physiopathology
  • Pedigree
  • Phenotype
  • RNA Splicing
  • Scoliosis / genetics*
  • Scoliosis / physiopathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Bbs7 protein, human
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Guanine Nucleotide Exchange Factors
  • RIN2 protein, human

Supplementary concepts

  • Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis