Novel homozygous sequence variants in the GDF5 gene underlie acromesomelic dysplasia type-grebe in consanguineous families

Congenit Anom (Kyoto). 2017 Mar;57(2):45-51. doi: 10.1111/cga.12187.

Abstract

Acromesomelic dysplasia Grebe type (AMDG) is characterized by severe knob like non-functional fingers and short acromesomelic limbs, and is inherited in an autosomal recessive manner. Disease causing sequence variants in the GDF5 (Growth Differentiation Factor 5) gene located on chromosome 20q11.22 are responsible for causing AMDG. In the study, presented here, two consanguineous families with AMDG were clinically and genetically characterized. After establishing linkage in the two families (A and B) to GDF5 gene on chromosome 20q11.22, Sanger DNA sequencing was performed in all available affected and unaffected members. Sequence analysis of the GDF5 gene revealed two novel variants including a duplication (c.157_158dupC, p.Leu53Profs*41) in family A, and a nonsense (p.Trp291*) in family B. Our findings extend the body of evidence that supports the importance of GDF5 in the development of limbs.

Keywords: GDF5 (CDMP1); acromesomelic dysplasia grebe type; genotyping; novel sequence variants.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Consanguinity*
  • Dwarfism / genetics*
  • Dwarfism / pathology
  • Female
  • Genetic Linkage
  • Growth Differentiation Factor 5 / genetics*
  • Homozygote
  • Humans
  • Male
  • Musculoskeletal Abnormalities / genetics*
  • Musculoskeletal Abnormalities / pathology
  • Mutation / genetics*
  • Osteochondrodysplasias / genetics*
  • Osteochondrodysplasias / pathology
  • Pedigree
  • Sequence Homology, Amino Acid
  • Young Adult

Substances

  • GDF5 protein, human
  • Growth Differentiation Factor 5

Supplementary concepts

  • Acromesomelic dysplasia
  • Chondrodysplasia, Grebe type