Recurrence of CCHS associated PHOX2B poly-alanine expansion mutation due to maternal mosaicism

Pediatr Pulmonol. 2014 Mar;49(3):E45-7. doi: 10.1002/ppul.22790. Epub 2013 Mar 4.

Abstract

Heterozygous in frame trinucleotide duplications within the PHOX2B gene, leading to poly-alanine expansions, cause Congenital Central Hypoventilation Syndrome. Here we report about a CCHS patient, carrying a +13Ala PHOX2B expansion, whose asymptomatic mother resulted with a low level of mosaicism for the same mutation in peripheral blood cells. Her second pregnancy ended with the spontaneous miscarriage of a fetus who had inherited the PHOX2B mutation, thus confirming germline mosaicism in the mother and the need of proper genetic counseling to CCHS families.

Keywords: PHOX2B polyalanine expansion; capillary electrophoresis of fluorescent amplimers; congenital central hypoventilation syndrome (CCHS); disease recurrence; genetic counseling; somatic mosaicism.

Publication types

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

MeSH terms

  • Abortion, Spontaneous / genetics*
  • Alanine
  • Electrophoresis, Capillary
  • Female
  • Genetic Counseling*
  • Germ-Line Mutation / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Hypoventilation / congenital*
  • Hypoventilation / genetics
  • Infant, Newborn
  • Male
  • Mosaicism*
  • Pregnancy
  • Sleep Apnea, Central / genetics*
  • Transcription Factors / genetics*
  • Trinucleotide Repeat Expansion / genetics*

Substances

  • Homeodomain Proteins
  • NBPhox protein
  • Transcription Factors
  • Alanine

Supplementary concepts

  • Congenital central hypoventilation syndrome