Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene
Abstract Background Homozygous or compound heterozygous PRUNE1 mutations cause a neurodevelopmental disorder with microcephaly, hypotonia, and variable brain malformations (NMIHBA) (OMIM #617481). The PRUNE1 gene encodes a member of the phosphoesterase (DHH) protein superfamily that is involved in t...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-022-01228-6 |
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| author | Mehdi Agha Gholizadeh Mina Mohammadi-Sarband Fatemeh Fardanesh Masoud Garshasbi |
| author_facet | Mehdi Agha Gholizadeh Mina Mohammadi-Sarband Fatemeh Fardanesh Masoud Garshasbi |
| author_sort | Mehdi Agha Gholizadeh |
| collection | DOAJ |
| description | Abstract Background Homozygous or compound heterozygous PRUNE1 mutations cause a neurodevelopmental disorder with microcephaly, hypotonia, and variable brain malformations (NMIHBA) (OMIM #617481). The PRUNE1 gene encodes a member of the phosphoesterase (DHH) protein superfamily that is involved in the regulation of cell migration. To date, most of the described mutations in the PRUNE1 gene are clustered in DHH domain. Methods We subjected 4 members (two affected and two healthy) of a consanguineous Iranian family in the study. The proband underwent whole-exome sequencing and a start loss identified variant was confirmed by Sanger sequencing. Co-segregation of the detected variant with the disease in family was confirmed. Results By whole-exome sequencing, we identified the a start loss variant, NM_021222.3:c.3G>A; p.(Met1?), in the PRUNE1 in two patients of a consanguineous Iranian family with spastic quadriplegic cerebral palsy (CP), hypotonia, developmental regression, and cerebellar atrophy. Sanger sequencing confirmed the segregation of the variant with the disease in the family. Protein structure analysis also revealed that the variant probably leads to the deletion of DHH (Asp-His-His) domain, the active site of the protein, and loss of PRUNE1 function. Conclusion We identified a start loss variant, NM_021222.3:c.3G>A; p.(Met1?) in the PRUNE1 gene in two affected members as a possible cause of NMIHBA in an Iranian family. We believe that the study adds a new pathogenic variant in spectrum of mutations in the PRUNE1 gene as a cause of PRUNE1-related syndrome. |
| first_indexed | 2024-12-10T15:13:18Z |
| format | Article |
| id | doaj.art-4aca95e8743e41c7b96526d7f9213199 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-10T15:13:18Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-4aca95e8743e41c7b96526d7f92131992022-12-22T01:43:53ZengBMCBMC Medical Genomics1755-87942022-04-0115111110.1186/s12920-022-01228-6Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 geneMehdi Agha Gholizadeh0Mina Mohammadi-Sarband1Fatemeh Fardanesh2Masoud Garshasbi3Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares UniversityShemiranat Genetic Counselling Center, State Welfare OrganizationShemiranat Genetic Counselling Center, State Welfare OrganizationDepartment of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares UniversityAbstract Background Homozygous or compound heterozygous PRUNE1 mutations cause a neurodevelopmental disorder with microcephaly, hypotonia, and variable brain malformations (NMIHBA) (OMIM #617481). The PRUNE1 gene encodes a member of the phosphoesterase (DHH) protein superfamily that is involved in the regulation of cell migration. To date, most of the described mutations in the PRUNE1 gene are clustered in DHH domain. Methods We subjected 4 members (two affected and two healthy) of a consanguineous Iranian family in the study. The proband underwent whole-exome sequencing and a start loss identified variant was confirmed by Sanger sequencing. Co-segregation of the detected variant with the disease in family was confirmed. Results By whole-exome sequencing, we identified the a start loss variant, NM_021222.3:c.3G>A; p.(Met1?), in the PRUNE1 in two patients of a consanguineous Iranian family with spastic quadriplegic cerebral palsy (CP), hypotonia, developmental regression, and cerebellar atrophy. Sanger sequencing confirmed the segregation of the variant with the disease in the family. Protein structure analysis also revealed that the variant probably leads to the deletion of DHH (Asp-His-His) domain, the active site of the protein, and loss of PRUNE1 function. Conclusion We identified a start loss variant, NM_021222.3:c.3G>A; p.(Met1?) in the PRUNE1 gene in two affected members as a possible cause of NMIHBA in an Iranian family. We believe that the study adds a new pathogenic variant in spectrum of mutations in the PRUNE1 gene as a cause of PRUNE1-related syndrome.https://doi.org/10.1186/s12920-022-01228-6PRUNE1Neurodevelopmental disorderNMIHBAWhole-exome sequencing |
| spellingShingle | Mehdi Agha Gholizadeh Mina Mohammadi-Sarband Fatemeh Fardanesh Masoud Garshasbi Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene BMC Medical Genomics PRUNE1 Neurodevelopmental disorder NMIHBA Whole-exome sequencing |
| title | Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene |
| title_full | Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene |
| title_fullStr | Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene |
| title_full_unstemmed | Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene |
| title_short | Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene |
| title_sort | neurodevelopmental disorder with microcephaly hypotonia and variable brain anomalies in a consanguineous iranian family is associated with a homozygous start loss variant in the prune1 gene |
| topic | PRUNE1 Neurodevelopmental disorder NMIHBA Whole-exome sequencing |
| url | https://doi.org/10.1186/s12920-022-01228-6 |
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