KIF1A novel frameshift variant p.(Ser887Profs*64) exhibits clinical heterogeneity in a Pakistani family with hereditary sensory and autonomic neuropathy type IIC.
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| Title: | KIF1A novel frameshift variant p.(Ser887Profs*64) exhibits clinical heterogeneity in a Pakistani family with hereditary sensory and autonomic neuropathy type IIC. |
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| Authors: | Ghafoor, Saima (AUTHOR), Rafiq, Muhammad Arshad (AUTHOR), Abbas Shah, Syed Tahir (AUTHOR), Ansar, Muhammad (AUTHOR), Paton, Tara (AUTHOR), Ajmal, Muhammad (AUTHOR), Agha, Zehra (AUTHOR), Qamar, Raheel (AUTHOR), Azam, Maleeha (AUTHOR) |
| Source: | International Journal of Neuroscience. Jun2024, Vol. 134 Issue 6, p665-675. 11p. |
| Subjects: | Single nucleotide polymorphisms, Frameshift mutation, Neuropathy, Genetic disorders, Peripheral nervous system |
| Abstract: | Background: Hereditary sensory and autonomic neuropathies (HSANs) are rare heterogeneous group of neurological disorders caused by peripheral nerve deterioration. The HSANs sub-clinical classes have clinical and genetic overlap which often lead to misdiagnosis. In the present study a Pakistani family with five affected members suffering from severe neuropathy were genetically analyzed to identify the disease causative element in the family. Methods: Genome wide high-density single nucleotide polymorphism (SNP) microarray analysis was carried out followed by whole exome sequencing of the affected proband and another affected sibling. Shared homozygous regions in all severely affected members were identified through homozygosity mapping approach. Results: The largest homozygous region of 14.1 Mb shared by the five severely affected members of the family was identified on chromosome 2. Subsequent exome sequencing identified a novel single nucleotide deletion c.2658del; p.(Ser887Profs*64) in KIF1A. Segregation analysis revealed that this mutation was homozygous in all five affected individuals of the family with severe clinical manifestation, while members of the family that were heterozygous carriers shared abnormal skin features (scaly skin) only with the homozygous affected members. Conclusions: A novel frameshift mutation p.(Ser887Profs*64) in KIF1A is the potential cause of severe HSANIIC in a Pakistani family along with incomplete penetrance in mutation carriers. We demonstrate that using a combination of different techniques not only strengthens the gene finding approach but also helps in proper sub-clinical characterization along with identification of mutated alleles exhibiting incomplete penetrance leading to intrafamilial clinical variability in HSAN group of inherited diseases. [ABSTRACT FROM AUTHOR] |
| Copyright of International Journal of Neuroscience is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 177520069 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: KIF1A novel frameshift variant p.(Ser887Profs*64) exhibits clinical heterogeneity in a Pakistani family with hereditary sensory and autonomic neuropathy type IIC. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Ghafoor%2C+Saima%22">Ghafoor, Saima</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rafiq%2C+Muhammad+Arshad%22">Rafiq, Muhammad Arshad</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Abbas+Shah%2C+Syed+Tahir%22">Abbas Shah, Syed Tahir</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ansar%2C+Muhammad%22">Ansar, Muhammad</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Paton%2C+Tara%22">Paton, Tara</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ajmal%2C+Muhammad%22">Ajmal, Muhammad</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Agha%2C+Zehra%22">Agha, Zehra</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Qamar%2C+Raheel%22">Qamar, Raheel</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Azam%2C+Maleeha%22">Azam, Maleeha</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Neuroscience%22">International Journal of Neuroscience</searchLink>. Jun2024, Vol. 134 Issue 6, p665-675. 11p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Single+nucleotide+polymorphisms%22">Single nucleotide polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Frameshift+mutation%22">Frameshift mutation</searchLink><br /><searchLink fieldCode="DE" term="%22Neuropathy%22">Neuropathy</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+disorders%22">Genetic disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Peripheral+nervous+system%22">Peripheral nervous system</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background: Hereditary sensory and autonomic neuropathies (HSANs) are rare heterogeneous group of neurological disorders caused by peripheral nerve deterioration. The HSANs sub-clinical classes have clinical and genetic overlap which often lead to misdiagnosis. In the present study a Pakistani family with five affected members suffering from severe neuropathy were genetically analyzed to identify the disease causative element in the family. Methods: Genome wide high-density single nucleotide polymorphism (SNP) microarray analysis was carried out followed by whole exome sequencing of the affected proband and another affected sibling. Shared homozygous regions in all severely affected members were identified through homozygosity mapping approach. Results: The largest homozygous region of 14.1 Mb shared by the five severely affected members of the family was identified on chromosome 2. Subsequent exome sequencing identified a novel single nucleotide deletion c.2658del; p.(Ser887Profs*64) in KIF1A. Segregation analysis revealed that this mutation was homozygous in all five affected individuals of the family with severe clinical manifestation, while members of the family that were heterozygous carriers shared abnormal skin features (scaly skin) only with the homozygous affected members. Conclusions: A novel frameshift mutation p.(Ser887Profs*64) in KIF1A is the potential cause of severe HSANIIC in a Pakistani family along with incomplete penetrance in mutation carriers. We demonstrate that using a combination of different techniques not only strengthens the gene finding approach but also helps in proper sub-clinical characterization along with identification of mutated alleles exhibiting incomplete penetrance leading to intrafamilial clinical variability in HSAN group of inherited diseases. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of International Journal of Neuroscience is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1080/00207454.2022.2140428 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 11 StartPage: 665 Subjects: – SubjectFull: Single nucleotide polymorphisms Type: general – SubjectFull: Frameshift mutation Type: general – SubjectFull: Neuropathy Type: general – SubjectFull: Genetic disorders Type: general – SubjectFull: Peripheral nervous system Type: general Titles: – TitleFull: KIF1A novel frameshift variant p.(Ser887Profs*64) exhibits clinical heterogeneity in a Pakistani family with hereditary sensory and autonomic neuropathy type IIC. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Ghafoor, Saima – PersonEntity: Name: NameFull: Rafiq, Muhammad Arshad – PersonEntity: Name: NameFull: Abbas Shah, Syed Tahir – PersonEntity: Name: NameFull: Ansar, Muhammad – PersonEntity: Name: NameFull: Paton, Tara – PersonEntity: Name: NameFull: Ajmal, Muhammad – PersonEntity: Name: NameFull: Agha, Zehra – PersonEntity: Name: NameFull: Qamar, Raheel – PersonEntity: Name: NameFull: Azam, Maleeha IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 06 Text: Jun2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 00207454 Numbering: – Type: volume Value: 134 – Type: issue Value: 6 Titles: – TitleFull: International Journal of Neuroscience Type: main |
| ResultId | 1 |
