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...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/218446d81b0a4deda8e7c1a821aa05c8 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:218446d81b0a4deda8e7c1a821aa05c8 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:218446d81b0a4deda8e7c1a821aa05c82021-12-02T17:41:28ZA homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy10.1038/s41598-021-92026-02045-2322https://doaj.org/article/218446d81b0a4deda8e7c1a821aa05c82021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92026-0https://doaj.org/toc/2045-2322Abstract 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.Kheloud M. AlhamoudiTlili BarhoumiHamad Al-EidiAbdulaziz AsiriMarwan NashabatManal AlaameryMasheal AlharbiYazeid AlhaidanBrahim TabarkiMuhammad UmairMajid AlfadhelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Kheloud M. Alhamoudi Tlili Barhoumi Hamad Al-Eidi Abdulaziz Asiri Marwan Nashabat Manal Alaamery Masheal Alharbi Yazeid Alhaidan Brahim Tabarki Muhammad Umair Majid Alfadhel A homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy |
| description |
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. |
| format |
article |
| author |
Kheloud M. Alhamoudi Tlili Barhoumi Hamad Al-Eidi Abdulaziz Asiri Marwan Nashabat Manal Alaamery Masheal Alharbi Yazeid Alhaidan Brahim Tabarki Muhammad Umair Majid Alfadhel |
| author_facet |
Kheloud M. Alhamoudi Tlili Barhoumi Hamad Al-Eidi Abdulaziz Asiri Marwan Nashabat Manal Alaamery Masheal Alharbi Yazeid Alhaidan Brahim Tabarki Muhammad Umair Majid Alfadhel |
| author_sort |
Kheloud M. Alhamoudi |
| title |
A homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy |
| title_short |
A homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy |
| title_full |
A homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy |
| title_fullStr |
A homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy |
| title_full_unstemmed |
A homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy |
| title_sort |
homozygous nonsense mutation in dcbld2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/218446d81b0a4deda8e7c1a821aa05c8 |
| work_keys_str_mv |
AT kheloudmalhamoudi ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT tlilibarhoumi ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT hamadaleidi ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT abdulazizasiri ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT marwannashabat ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT manalalaamery ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT mashealalharbi ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT yazeidalhaidan ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT brahimtabarki ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT muhammadumair ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT majidalfadhel ahomozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT kheloudmalhamoudi homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT tlilibarhoumi homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT hamadaleidi homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT abdulazizasiri homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT marwannashabat homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT manalalaamery homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT mashealalharbi homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT yazeidalhaidan homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT brahimtabarki homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT muhammadumair homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy AT majidalfadhel homozygousnonsensemutationindcbld2isacandidatecauseofdevelopmentaldelaydysmorphicfeaturesandrestrictivecardiomyopathy |
| _version_ |
1718379633666162688 |