Novel FREM1 mutations in a patient with MOTA syndrome: Clinical findings, mutation update and review of FREM1-related disorders literature

Eur J Med Genet. 2017 Mar;60(3):190-194. doi: 10.1016/j.ejmg.2017.01.005. Epub 2017 Jan 19.

Abstract

Manitoba-oculo-tricho-anal (MOTA) syndrome is an uncommon condition arising from biallelic mutations of FREM1 gene and clinically characterized by a variable spectrum of eyelid malformations, aberrant hairline, bifid or broad nasal tip, and gastrointestinal anomalies. In this report, we describe a patient with a phenotype compatible with MOTA syndrome (aberrant anterior hair line, hypertelorism, unilateral anophthalmia, and bifid and broad nasal tip) in whom two novel FREM1 mutations (c.305 A > G, p.Asp102Gly; and c.2626delG, p.Val876Tyrfs*16) were identified in the compound heterozygous state, thus broadening the mutational spectrum of the disease. We performed a literature review of the clinical and genetic features of individuals carrying FREM1 mutations.

Keywords: Aberrant hairline; Anal malformations; Anophthalmia; Bifid nasal tip; Coloboma; Cryptophthalmos; Eyelid malformations; FREM1; Hypertelorism; MOTA syndrome; Manitoba-oculo-tricho-anal syndrome.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Anal Canal / abnormalities*
  • Child, Preschool
  • Coloboma / genetics*
  • Eyelids / abnormalities
  • Female
  • Humans
  • Hypertelorism / genetics*
  • Phenotype
  • Receptors, Interleukin / genetics*

Substances

  • Frem1 protein, human
  • Receptors, Interleukin

Supplementary concepts

  • Marles Greenberg Persaud syndrome