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<p>Protein glycosylation defects can present with early-onset brain malformations and muscular dystrophy or milder, late-onset muscular dystrophy. Here, we report a new glycosylation defect with an atypical phenotype of late-onset, progressive, severe brain atrophy and muscular dystrophy in a 47-year-old man. Exome sequencing revealed a homozygous highly deleterious c.478G&gt;T (p.G160W) variant in the <i>B3GNT4</i> gene. A knock-in mouse model replicated the patient’s muscle histology. B3GNT4 is expressed at very low levels in the thalamus, and this region was selectively preserved in the patient. The study demonstrates the first disease associated with one of the seven B3GNT galactosyltransferases and the importance of B3GNT4 in adolescence to adult muscle and CNS development.</p>

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A homozygous variant in the beta-1,3-N-acetylglucosaminyltransferase 4 gene causes progressive brain atrophy and muscular dystrophy

  • 期刊论文

  • 发表日期：

    2025年12月24日

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  • John Vissing,
  • Ana Töpf,
  • Volker Straub,
  • Thomas Krag

摘要

Protein glycosylation defects can present with early-onset brain malformations and muscular dystrophy or milder, late-onset muscular dystrophy. Here, we report a new glycosylation defect with an atypical phenotype of late-onset, progressive, severe brain atrophy and muscular dystrophy in a 47-year-old man. Exome sequencing revealed a homozygous highly deleterious c.478G>T (p.G160W) variant in the B3GNT4 gene. A knock-in mouse model replicated the patient’s muscle histology. B3GNT4 is expressed at very low levels in the thalamus, and this region was selectively preserved in the patient. The study demonstrates the first disease associated with one of the seven B3GNT galactosyltransferases and the importance of B3GNT4 in adolescence to adult muscle and CNS development.