Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect

Area of Science:

• Genetics
• Neuroscience
• Biochemistry

Background:

• The MBOAT7 gene encodes an enzyme crucial for phosphoinositol phosphate remodeling within the LANDs cycle.
• Mutations in MBOAT7 define a newly identified phospholipid remodeling disease.
• This is the second reported case series on MBOAT7 gene defects.

Purpose of the Study:

• To present comprehensive clinical, neuroimaging, and genetic data from patients with MBOAT7 gene defects.
• To characterize the phenotype associated with MBOAT7 mutations.
• To establish diagnostic indicators for this novel genetic disorder.

Main Methods:

• Clinical assessment of 12 patients from 7 families.
• Neuroimaging analysis (MRI).
• Genome-wide genotyping and exome sequencing to identify MBOAT7 mutations.

Main Results:

• Patients exhibited global developmental delay (speech/language), intellectual disability, ataxia, early-onset epilepsy, strabismus, and distinct facial features.
• Neuroimaging revealed cerebellar folial dysgenesis, cerebellar atrophy, globus pallidus/dentate nucleus T2 hyperintensities, enlarged perivascular spaces, and corpus callosum thinning.
• Five distinct homozygous MBOAT7 mutations were identified: p.Arg87*, p.Leu227ProfsX65, p.Gln376Lys, p.Trp426*, and a large deletion (chr19:54.666.173-54.677.766/11594 bp del).

Conclusions:

• Clinical and neuroimaging findings are suggestive of MBOAT7 gene defects.
• These characteristic features can guide genetic testing for accurate diagnosis.
• Understanding MBOAT7's role aids in diagnosing this phospholipid remodeling disease.