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Introduction <p>Pathogenic variants in several genes are responsible for global developmental delay and intellectual disability. Many of them cause synaptic signalling dysregulation. Clathrin-mediated endocytosis is involved in synaptic vesicle recycling and pathogenic variants in the <i>CLTC</i> gene, encoding clathrin heavy chain 1 are associated with delayed development and cognitive difficulties. Our aim is to widen the genotypic and phenotypic spectra of the <i>CLTC</i>-related disorders by reporting two new patients.</p> Methods <p>Gene panel sequencing was performed for the probands and the parents were tested for the variants found likely pathogenic in the probands.</p> Results <p>Novel, likely pathogenic variants in the <i>CLTC</i> gene were found in two patients. One of them, a boy had a heterozygous <i>de novo</i> missense variant. The other patient, a girl was the offspring of two siblings; both of whom carried the same heterozygous truncating variant as their daughter. All the patients were characterized by global developmental delay, intellectual disability and dysmorphic features.</p> Conclusions <p>The spectrum of <i>CLTC</i> variants, causing intellectual developmental disorder 56 (OMIM 617854) has been expanded by two novel variants. The range of the heterogeneous clinical findings caused by mutations in this gene has also been widened. A brief review of the mutations found in <i>CLTC</i> and clinical features related to these mutations are provided.</p>

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Intellectual developmental disorder 56 associated with novel variants in the clathrin heavy chain encoding CLTC gene and brief review of the literature

  • 期刊论文

  • 发表日期：

    2025年10月15日

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  • Tibor Kalmár,
  • Viktor Vedelek,
  • Zoltán Maróti,
  • Marianna Csenki,
  • László Sztriha

摘要

Introduction

Pathogenic variants in several genes are responsible for global developmental delay and intellectual disability. Many of them cause synaptic signalling dysregulation. Clathrin-mediated endocytosis is involved in synaptic vesicle recycling and pathogenic variants in the CLTC gene, encoding clathrin heavy chain 1 are associated with delayed development and cognitive difficulties. Our aim is to widen the genotypic and phenotypic spectra of the CLTC-related disorders by reporting two new patients.

Methods

Gene panel sequencing was performed for the probands and the parents were tested for the variants found likely pathogenic in the probands.

Results

Novel, likely pathogenic variants in the CLTC gene were found in two patients. One of them, a boy had a heterozygous de novo missense variant. The other patient, a girl was the offspring of two siblings; both of whom carried the same heterozygous truncating variant as their daughter. All the patients were characterized by global developmental delay, intellectual disability and dysmorphic features.

Conclusions

The spectrum of CLTC variants, causing intellectual developmental disorder 56 (OMIM 617854) has been expanded by two novel variants. The range of the heterogeneous clinical findings caused by mutations in this gene has also been widened. A brief review of the mutations found in CLTC and clinical features related to these mutations are provided.