A patient with novel MBOAT7 variant: The cerebellar atrophy is progressive and displays a peculiar neurometabolic profile

Am J Med Genet A. 2020 Oct;182(10):2377-2383. doi: 10.1002/ajmg.a.61773. Epub 2020 Aug 3.


Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5-year-old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole-exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen-magnetic resonance spectroscopy (H-MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7-related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth.

Keywords: MBOAT7; cerebellar atrophy; consanguinity; hydrogen-magnetic resonance spectroscopy; intellectual disability; review.

Publication types

  • Case Reports

MeSH terms

  • Acyltransferases / genetics*
  • Adolescent
  • Adult
  • Cerebellum / diagnostic imaging
  • Child
  • Consanguinity
  • Exome / genetics
  • Exome Sequencing
  • Female
  • Genetic Predisposition to Disease*
  • Homozygote
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Membrane Proteins / genetics*
  • Olivopontocerebellar Atrophies / genetics*
  • Olivopontocerebellar Atrophies / pathology
  • Pedigree
  • Young Adult


  • Membrane Proteins
  • Acyltransferases
  • MBOAT7 protein, human

Supplementary concepts

  • Pontocerebellar Hypoplasia Type 3