A homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy
Abstract DCBLD2 encodes discodin, CUB and LCCL domain-containing protein 2, a type-I transmembrane receptor that is involved in intracellular receptor signalling pathways and the regulation of cell growth. In this report, we describe a 5-year-old female who presented severe clinical features, includ...
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| Autores principales: | , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/218446d81b0a4deda8e7c1a821aa05c8 |
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| Sumario: | Abstract DCBLD2 encodes discodin, CUB and LCCL domain-containing protein 2, a type-I transmembrane receptor that is involved in intracellular receptor signalling pathways and the regulation of cell growth. In this report, we describe a 5-year-old female who presented severe clinical features, including restrictive cardiomyopathy, developmental delay, spasticity and dysmorphic features. Trio-whole-exome sequencing and segregation analysis were performed to identify the genetic cause of the disease within the family. A novel homozygous nonsense variant in the DCBLD2 gene (c.80G > A, p.W27*) was identified as the most likely cause of the patient’s phenotype. This nonsense variant falls in the extracellular N-terminus of DCBLD2 and thus might affect proper protein function of the transmembrane receptor. A number of in vitro investigations were performed on the proband’s skin fibroblasts compared to normal fibroblasts, which allowed a comprehensive assessment resulting in the functional characterization of the identified DCBLD2 nonsense variant in different cellular processes. Our data propose a significant association between the identified variant and the observed reduction in cell proliferation, cell cycle progression, intracellular ROS, and Ca2 + levels, which would likely explain the phenotypic presentation of the patient as associated with lethal restrictive cardiomyopathy. |
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