Somatic mosaicism in trichorhinophalangeal syndrome: a lesson for genetic counseling

Eur J Hum Genet. 2014 Jan;22(1):136-9. doi: 10.1038/ejhg.2013.56. Epub 2013 Apr 10.

Abstract

Trichorhinophalangeal syndrome type I (TRPSI) is a genetic disorder characterized by sparse hair, a bulbous nasal tip, short stature with severe generalized shortening of all phalanges, metacarpal and metatarsal bones and cone-shaped epiphyses. This syndrome is caused by autosomal dominant mutations in the TRPS1 gene. However, because recurrence has been observed in siblings from healthy parents, an autosomal recessive mode of inheritance has also been suggested. We report on a male patient, born to healthy unrelated parents, with TRPSI. Using Sanger sequencing, we identified a mutation in the TRPS1 gene (c.2735 G>A, P.Cys912Tyr). The same mutation was detected as a 10% mosaic mutation by Pyrosequencing in blood-derived DNA from his healthy mother. To our knowledge, this is the first time that somatic mosaicism has been identified in TRPSI. This data combined with the observations of recurrences in siblings from healthy parents modifies the genetic counseling for TRPSI, which should discuss a 5-10 percent recurrence risk for healthy parents with an affected child because of the possibility of germinal mosaicism.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Child
  • DNA-Binding Proteins / genetics*
  • Fingers / abnormalities*
  • Fingers / pathology
  • Genetic Counseling*
  • Hair Diseases / genetics*
  • Hair Diseases / pathology
  • Humans
  • Langer-Giedion Syndrome / genetics*
  • Langer-Giedion Syndrome / pathology
  • Male
  • Mosaicism
  • Nose / abnormalities*
  • Nose / pathology
  • Repressor Proteins
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • Repressor Proteins
  • TRPS1 protein, human
  • Transcription Factors

Supplementary concepts

  • Trichorhinophalangeal Syndrome, Type I