Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations

Am J Med Genet A. 2016 Jan;170A(1):210-6. doi: 10.1002/ajmg.a.37393. Epub 2015 Sep 16.

Abstract

Primordial dwarfism encompasses rare conditions characterized by severe intrauterine growth retardation and growth deficiency throughout life. Recently, three POC1A mutations have been reported in six families with the primordial dwarfism, SOFT syndrome (Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis). Using a custom-designed Next-generation sequencing skeletal dysplasia panel, we have identified two novel homozygous POC1A mutations in two individuals with primordial dwarfism. The severe growth retardation and the facial profiles are strikingly similar between our patients and those described previously. However, one of our patients was diagnosed with severe foramen magnum stenosis and subglottic tracheal stenosis, malformations not previously associated with this syndrome. Our findings confirm that POC1A mutations cause SOFT syndrome and that mutations in this gene should be considered in patients with severe pre- and postnatal short stature, symmetric shortening of long bones, triangular facies, sparse hair and short, thickened distal phalanges.

Keywords: POC1A; SOFT syndrome; centriole; primordial dwarfism; skeletal dysplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adolescent
  • Cell Cycle Proteins
  • Craniofacial Abnormalities / genetics*
  • Cytoskeletal Proteins
  • Dwarfism / genetics*
  • Humans
  • Hypotrichosis / genetics*
  • Infant
  • Male
  • Muscular Atrophy / genetics*
  • Nail Diseases / congenital
  • Nail Diseases / genetics*
  • Osteochondrodysplasias / genetics*
  • Proteins / genetics*
  • Thorax / abnormalities

Substances

  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • POC1A protein, human
  • Proteins

Supplementary concepts

  • Facial Dysmorphism with Multiple Malformations