Novel PPP1R21 mutation in a family with autosomal recessive neurodevelopmental disorder: results of genomics and molecular analysis
Abstract Background Neurodevelopmental diseases are a group of disorders affecting the development of the nervous system and brain function. In particular, neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities is a novel neurodevelopmental syndrome caused by biallel...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-10-01
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| Series: | Egyptian Journal of Medical Human Genetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43042-023-00444-8 |
| _version_ | 1827710716227878912 |
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| author | Donya Ghazi-Nader Behnam Karimi Reza Alibakhshi Maziar Ganji |
| author_facet | Donya Ghazi-Nader Behnam Karimi Reza Alibakhshi Maziar Ganji |
| author_sort | Donya Ghazi-Nader |
| collection | DOAJ |
| description | Abstract Background Neurodevelopmental diseases are a group of disorders affecting the development of the nervous system and brain function. In particular, neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities is a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss-of-function variants. This study aimed to investigate the molecular etiology of this neurodevelopmental disorder in an Iranian patient from a consanguineous marriage family. Methods and results After clinical examination and DNA sampling, whole exome sequencing was performed for the patient. The findings were confirmed and segregated via Sanger sequencing and bioinformatics approach in the patient and parents, respectively. We identified the novel loss-of-function mutation of c.1317_1318delAG p.(Asp440Tyrfs*6) in PPP1R21 gene in our patient suffering from severe developmental delays, mental retardation, facial deformities, muscle weakness, difficulty breathing and feeding, and vision impairment. Through Sanger sequencing, the homozygous and heterozygous statuses of this variant were observed in the patient and the parents, respectively. As well, the bioinformatics approach demonstrated the disease-causing effect and clinical pathogenicity of this mutation. Conclusions Such findings improve our knowledge of patients with neurodevelopmental phenotypes. In addition, these results can be particularly helpful for prenatal and preimplantation diagnosis and genetic counseling of families with a high risk of infantile intellectual disabilities. |
| first_indexed | 2024-03-10T17:42:43Z |
| format | Article |
| id | doaj.art-552004d848e04aa9b2903ea27971bb9e |
| institution | Directory Open Access Journal |
| issn | 2090-2441 |
| language | English |
| last_indexed | 2024-03-10T17:42:43Z |
| publishDate | 2023-10-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj.art-552004d848e04aa9b2903ea27971bb9e2023-11-20T09:37:54ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412023-10-012411910.1186/s43042-023-00444-8Novel PPP1R21 mutation in a family with autosomal recessive neurodevelopmental disorder: results of genomics and molecular analysisDonya Ghazi-Nader0Behnam Karimi1Reza Alibakhshi2Maziar Ganji3Dr. Alibakhshi Medical Genetics LaboratoryDr. Alibakhshi Medical Genetics LaboratoryDr. Alibakhshi Medical Genetics LaboratoryDepartment of Biological Sciences, The University of MemphisAbstract Background Neurodevelopmental diseases are a group of disorders affecting the development of the nervous system and brain function. In particular, neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities is a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss-of-function variants. This study aimed to investigate the molecular etiology of this neurodevelopmental disorder in an Iranian patient from a consanguineous marriage family. Methods and results After clinical examination and DNA sampling, whole exome sequencing was performed for the patient. The findings were confirmed and segregated via Sanger sequencing and bioinformatics approach in the patient and parents, respectively. We identified the novel loss-of-function mutation of c.1317_1318delAG p.(Asp440Tyrfs*6) in PPP1R21 gene in our patient suffering from severe developmental delays, mental retardation, facial deformities, muscle weakness, difficulty breathing and feeding, and vision impairment. Through Sanger sequencing, the homozygous and heterozygous statuses of this variant were observed in the patient and the parents, respectively. As well, the bioinformatics approach demonstrated the disease-causing effect and clinical pathogenicity of this mutation. Conclusions Such findings improve our knowledge of patients with neurodevelopmental phenotypes. In addition, these results can be particularly helpful for prenatal and preimplantation diagnosis and genetic counseling of families with a high risk of infantile intellectual disabilities.https://doi.org/10.1186/s43042-023-00444-8PPP1R21Neurodevelopmental disorderWhole exome sequencing |
| spellingShingle | Donya Ghazi-Nader Behnam Karimi Reza Alibakhshi Maziar Ganji Novel PPP1R21 mutation in a family with autosomal recessive neurodevelopmental disorder: results of genomics and molecular analysis Egyptian Journal of Medical Human Genetics PPP1R21 Neurodevelopmental disorder Whole exome sequencing |
| title | Novel PPP1R21 mutation in a family with autosomal recessive neurodevelopmental disorder: results of genomics and molecular analysis |
| title_full | Novel PPP1R21 mutation in a family with autosomal recessive neurodevelopmental disorder: results of genomics and molecular analysis |
| title_fullStr | Novel PPP1R21 mutation in a family with autosomal recessive neurodevelopmental disorder: results of genomics and molecular analysis |
| title_full_unstemmed | Novel PPP1R21 mutation in a family with autosomal recessive neurodevelopmental disorder: results of genomics and molecular analysis |
| title_short | Novel PPP1R21 mutation in a family with autosomal recessive neurodevelopmental disorder: results of genomics and molecular analysis |
| title_sort | novel ppp1r21 mutation in a family with autosomal recessive neurodevelopmental disorder results of genomics and molecular analysis |
| topic | PPP1R21 Neurodevelopmental disorder Whole exome sequencing |
| url | https://doi.org/10.1186/s43042-023-00444-8 |
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