Heterogeneity of comprehensive clinical phenotype and longitudinal adaptive function and correlation with computational predictions of severity of missense genotypes in KIF1A-associated neurological disorder
Pathogenic variants in kinesin family member 1A (KIF1A) are associated with KIF1A-associated neurological disorder. We report the clinical phenotypes and correlate genotypes of individuals with KIF1A-associated neurological disorder. Medical history and adaptive function were assessed longitudinally...
Gespeichert in:
Veröffentlicht in: | Genetics in medicine 2024-08, Vol.26 (8), p.101169, Article 101169 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 8 |
container_start_page | 101169 |
container_title | Genetics in medicine |
container_volume | 26 |
creator | Sudnawa, Khemika K. Li, Wenxing Calamia, Sean Kanner, Cara H. Bain, Jennifer M. Abdelhakim, Aliaa H. Geltzeiler, Alexa Mebane, Caroline M. Provenzano, Frank A. Sands, Tristan T. Fee, Robert J. Montes, Jacqueline Shen, Yufeng Chung, Wendy K. |
description | Pathogenic variants in kinesin family member 1A (KIF1A) are associated with KIF1A-associated neurological disorder. We report the clinical phenotypes and correlate genotypes of individuals with KIF1A-associated neurological disorder.
Medical history and adaptive function were assessed longitudinally. In-person evaluations included neurological, motor, ophthalmologic, and cognitive assessments.
We collected online data on 177 individuals. Fifty-seven individuals were also assessed in-person. Most individuals had de novo heterozygous missense likely pathogenic/pathogenic KIF1A variants. The most common characteristics were hypotonia, spasticity, ataxia, seizures, optic nerve atrophy, cerebellar atrophy, and cognitive impairment. Mean Vineland adaptive behavior composite score (VABS-ABC) was low (M = 62.9, SD = 19.1). The mean change in VABS-ABC over time was −3.1 (SD = 7.3). The decline in VABS-ABC was associated with the age at first assessment and abnormal electroencephalogram/seizure. There was a positive correlation between evolutionary scale model (ESM) score for the variants and final VABS-ABC (P = .003). Abnormal electroencephalogram/seizure, neuroimaging result, and ESM explain 34% of the variance in final VABS-ABC (P < .001).
In-person assessment confirmed caregiver report and identified additional visual deficits. Adaptive function declined over time consistent with both the neurodevelopmental and neurodegenerative nature of the condition. Using ESM score assists in predicting phenotype across a wide range of unique variants.
[Display omitted] |
doi_str_mv | 10.1016/j.gim.2024.101169 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3060380365</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1098360024001035</els_id><sourcerecordid>3060380365</sourcerecordid><originalsourceid>FETCH-LOGICAL-c278t-aac41b4ef695355bea3f3de91a810968bc675c2078a58085621b30a7d71e86da3</originalsourceid><addsrcrecordid>eNp9kc9u3CAQxlHVqvnTPkAvFcdevAWzYFY9RVHTRI3US3tGGMYOKxtcwBvtU_aVir2bHnuCGX7zzTAfQh8o2VBCxef9pnfjpib1domp2L1Cl5QzUhEmxOtyJztZMUHIBbpKaU8IbVhN3qILJhvJqdheoj_3kCGGHjy4fMShwyaMU4Qn8MkdAJvBeWf0gKeSCfk4Adbe4iH43uXZOl-etNVTXuBu9ia74FfEhBhh0Gv87PLTKjznNbHoRbBupdPSNcEB4nmC0aVU2gPuzy0Tdh5_f7ijN5VOKRinM1jsYY5hCP06nnUpRAvxHXrT6SHB-_N5jX7dff15e189_vj2cHvzWJm6kbnS2mxpu4VO7DjjvAXNOmZhR7UsSxOyNaLhpiaN1FwSyUVNW0Z0YxsKUljNrtGnk-4Uw-8ZUlZlagPDoD2EOSlGBGGy-MALSk-oiSGlCJ2aoht1PCpK1OKj2qvio1p8VCcfS83Hs_zcjmD_VbwYV4AvJwDKJw8OokrGgTdlqRFMVja4_8j_BQTbtM4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3060380365</pqid></control><display><type>article</type><title>Heterogeneity of comprehensive clinical phenotype and longitudinal adaptive function and correlation with computational predictions of severity of missense genotypes in KIF1A-associated neurological disorder</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Sudnawa, Khemika K. ; Li, Wenxing ; Calamia, Sean ; Kanner, Cara H. ; Bain, Jennifer M. ; Abdelhakim, Aliaa H. ; Geltzeiler, Alexa ; Mebane, Caroline M. ; Provenzano, Frank A. ; Sands, Tristan T. ; Fee, Robert J. ; Montes, Jacqueline ; Shen, Yufeng ; Chung, Wendy K.</creator><creatorcontrib>Sudnawa, Khemika K. ; Li, Wenxing ; Calamia, Sean ; Kanner, Cara H. ; Bain, Jennifer M. ; Abdelhakim, Aliaa H. ; Geltzeiler, Alexa ; Mebane, Caroline M. ; Provenzano, Frank A. ; Sands, Tristan T. ; Fee, Robert J. ; Montes, Jacqueline ; Shen, Yufeng ; Chung, Wendy K.</creatorcontrib><description>Pathogenic variants in kinesin family member 1A (KIF1A) are associated with KIF1A-associated neurological disorder. We report the clinical phenotypes and correlate genotypes of individuals with KIF1A-associated neurological disorder.
Medical history and adaptive function were assessed longitudinally. In-person evaluations included neurological, motor, ophthalmologic, and cognitive assessments.
We collected online data on 177 individuals. Fifty-seven individuals were also assessed in-person. Most individuals had de novo heterozygous missense likely pathogenic/pathogenic KIF1A variants. The most common characteristics were hypotonia, spasticity, ataxia, seizures, optic nerve atrophy, cerebellar atrophy, and cognitive impairment. Mean Vineland adaptive behavior composite score (VABS-ABC) was low (M = 62.9, SD = 19.1). The mean change in VABS-ABC over time was −3.1 (SD = 7.3). The decline in VABS-ABC was associated with the age at first assessment and abnormal electroencephalogram/seizure. There was a positive correlation between evolutionary scale model (ESM) score for the variants and final VABS-ABC (P = .003). Abnormal electroencephalogram/seizure, neuroimaging result, and ESM explain 34% of the variance in final VABS-ABC (P < .001).
In-person assessment confirmed caregiver report and identified additional visual deficits. Adaptive function declined over time consistent with both the neurodevelopmental and neurodegenerative nature of the condition. Using ESM score assists in predicting phenotype across a wide range of unique variants.
[Display omitted]</description><identifier>ISSN: 1098-3600</identifier><identifier>ISSN: 1530-0366</identifier><identifier>EISSN: 1530-0366</identifier><identifier>DOI: 10.1016/j.gim.2024.101169</identifier><identifier>PMID: 38785164</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adaptive function ; Adolescent ; Adult ; Child ; Child, Preschool ; Cognitive impairment ; Electroencephalography ; ESM ; Female ; Genotype ; Humans ; Infant ; KIF1A ; Kinesins - genetics ; Longitudinal Studies ; Male ; Middle Aged ; Mutation, Missense - genetics ; Nervous System Diseases - genetics ; Nervous System Diseases - pathology ; Nervous System Diseases - physiopathology ; Neurological disorder ; Phenotype ; Seizures - genetics ; Seizures - physiopathology ; Young Adult</subject><ispartof>Genetics in medicine, 2024-08, Vol.26 (8), p.101169, Article 101169</ispartof><rights>2024 American College of Medical Genetics and Genomics</rights><rights>Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c278t-aac41b4ef695355bea3f3de91a810968bc675c2078a58085621b30a7d71e86da3</cites><orcidid>0000-0003-3438-5685 ; 0000-0003-3576-5217</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38785164$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sudnawa, Khemika K.</creatorcontrib><creatorcontrib>Li, Wenxing</creatorcontrib><creatorcontrib>Calamia, Sean</creatorcontrib><creatorcontrib>Kanner, Cara H.</creatorcontrib><creatorcontrib>Bain, Jennifer M.</creatorcontrib><creatorcontrib>Abdelhakim, Aliaa H.</creatorcontrib><creatorcontrib>Geltzeiler, Alexa</creatorcontrib><creatorcontrib>Mebane, Caroline M.</creatorcontrib><creatorcontrib>Provenzano, Frank A.</creatorcontrib><creatorcontrib>Sands, Tristan T.</creatorcontrib><creatorcontrib>Fee, Robert J.</creatorcontrib><creatorcontrib>Montes, Jacqueline</creatorcontrib><creatorcontrib>Shen, Yufeng</creatorcontrib><creatorcontrib>Chung, Wendy K.</creatorcontrib><title>Heterogeneity of comprehensive clinical phenotype and longitudinal adaptive function and correlation with computational predictions of severity of missense genotypes in KIF1A-associated neurological disorder</title><title>Genetics in medicine</title><addtitle>Genet Med</addtitle><description>Pathogenic variants in kinesin family member 1A (KIF1A) are associated with KIF1A-associated neurological disorder. We report the clinical phenotypes and correlate genotypes of individuals with KIF1A-associated neurological disorder.
Medical history and adaptive function were assessed longitudinally. In-person evaluations included neurological, motor, ophthalmologic, and cognitive assessments.
We collected online data on 177 individuals. Fifty-seven individuals were also assessed in-person. Most individuals had de novo heterozygous missense likely pathogenic/pathogenic KIF1A variants. The most common characteristics were hypotonia, spasticity, ataxia, seizures, optic nerve atrophy, cerebellar atrophy, and cognitive impairment. Mean Vineland adaptive behavior composite score (VABS-ABC) was low (M = 62.9, SD = 19.1). The mean change in VABS-ABC over time was −3.1 (SD = 7.3). The decline in VABS-ABC was associated with the age at first assessment and abnormal electroencephalogram/seizure. There was a positive correlation between evolutionary scale model (ESM) score for the variants and final VABS-ABC (P = .003). Abnormal electroencephalogram/seizure, neuroimaging result, and ESM explain 34% of the variance in final VABS-ABC (P < .001).
In-person assessment confirmed caregiver report and identified additional visual deficits. Adaptive function declined over time consistent with both the neurodevelopmental and neurodegenerative nature of the condition. Using ESM score assists in predicting phenotype across a wide range of unique variants.
[Display omitted]</description><subject>Adaptive function</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cognitive impairment</subject><subject>Electroencephalography</subject><subject>ESM</subject><subject>Female</subject><subject>Genotype</subject><subject>Humans</subject><subject>Infant</subject><subject>KIF1A</subject><subject>Kinesins - genetics</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation, Missense - genetics</subject><subject>Nervous System Diseases - genetics</subject><subject>Nervous System Diseases - pathology</subject><subject>Nervous System Diseases - physiopathology</subject><subject>Neurological disorder</subject><subject>Phenotype</subject><subject>Seizures - genetics</subject><subject>Seizures - physiopathology</subject><subject>Young Adult</subject><issn>1098-3600</issn><issn>1530-0366</issn><issn>1530-0366</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u3CAQxlHVqvnTPkAvFcdevAWzYFY9RVHTRI3US3tGGMYOKxtcwBvtU_aVir2bHnuCGX7zzTAfQh8o2VBCxef9pnfjpib1domp2L1Cl5QzUhEmxOtyJztZMUHIBbpKaU8IbVhN3qILJhvJqdheoj_3kCGGHjy4fMShwyaMU4Qn8MkdAJvBeWf0gKeSCfk4Adbe4iH43uXZOl-etNVTXuBu9ia74FfEhBhh0Gv87PLTKjznNbHoRbBupdPSNcEB4nmC0aVU2gPuzy0Tdh5_f7ijN5VOKRinM1jsYY5hCP06nnUpRAvxHXrT6SHB-_N5jX7dff15e189_vj2cHvzWJm6kbnS2mxpu4VO7DjjvAXNOmZhR7UsSxOyNaLhpiaN1FwSyUVNW0Z0YxsKUljNrtGnk-4Uw-8ZUlZlagPDoD2EOSlGBGGy-MALSk-oiSGlCJ2aoht1PCpK1OKj2qvio1p8VCcfS83Hs_zcjmD_VbwYV4AvJwDKJw8OokrGgTdlqRFMVja4_8j_BQTbtM4</recordid><startdate>202408</startdate><enddate>202408</enddate><creator>Sudnawa, Khemika K.</creator><creator>Li, Wenxing</creator><creator>Calamia, Sean</creator><creator>Kanner, Cara H.</creator><creator>Bain, Jennifer M.</creator><creator>Abdelhakim, Aliaa H.</creator><creator>Geltzeiler, Alexa</creator><creator>Mebane, Caroline M.</creator><creator>Provenzano, Frank A.</creator><creator>Sands, Tristan T.</creator><creator>Fee, Robert J.</creator><creator>Montes, Jacqueline</creator><creator>Shen, Yufeng</creator><creator>Chung, Wendy K.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3438-5685</orcidid><orcidid>https://orcid.org/0000-0003-3576-5217</orcidid></search><sort><creationdate>202408</creationdate><title>Heterogeneity of comprehensive clinical phenotype and longitudinal adaptive function and correlation with computational predictions of severity of missense genotypes in KIF1A-associated neurological disorder</title><author>Sudnawa, Khemika K. ; Li, Wenxing ; Calamia, Sean ; Kanner, Cara H. ; Bain, Jennifer M. ; Abdelhakim, Aliaa H. ; Geltzeiler, Alexa ; Mebane, Caroline M. ; Provenzano, Frank A. ; Sands, Tristan T. ; Fee, Robert J. ; Montes, Jacqueline ; Shen, Yufeng ; Chung, Wendy K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c278t-aac41b4ef695355bea3f3de91a810968bc675c2078a58085621b30a7d71e86da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adaptive function</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cognitive impairment</topic><topic>Electroencephalography</topic><topic>ESM</topic><topic>Female</topic><topic>Genotype</topic><topic>Humans</topic><topic>Infant</topic><topic>KIF1A</topic><topic>Kinesins - genetics</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation, Missense - genetics</topic><topic>Nervous System Diseases - genetics</topic><topic>Nervous System Diseases - pathology</topic><topic>Nervous System Diseases - physiopathology</topic><topic>Neurological disorder</topic><topic>Phenotype</topic><topic>Seizures - genetics</topic><topic>Seizures - physiopathology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sudnawa, Khemika K.</creatorcontrib><creatorcontrib>Li, Wenxing</creatorcontrib><creatorcontrib>Calamia, Sean</creatorcontrib><creatorcontrib>Kanner, Cara H.</creatorcontrib><creatorcontrib>Bain, Jennifer M.</creatorcontrib><creatorcontrib>Abdelhakim, Aliaa H.</creatorcontrib><creatorcontrib>Geltzeiler, Alexa</creatorcontrib><creatorcontrib>Mebane, Caroline M.</creatorcontrib><creatorcontrib>Provenzano, Frank A.</creatorcontrib><creatorcontrib>Sands, Tristan T.</creatorcontrib><creatorcontrib>Fee, Robert J.</creatorcontrib><creatorcontrib>Montes, Jacqueline</creatorcontrib><creatorcontrib>Shen, Yufeng</creatorcontrib><creatorcontrib>Chung, Wendy K.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Genetics in medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sudnawa, Khemika K.</au><au>Li, Wenxing</au><au>Calamia, Sean</au><au>Kanner, Cara H.</au><au>Bain, Jennifer M.</au><au>Abdelhakim, Aliaa H.</au><au>Geltzeiler, Alexa</au><au>Mebane, Caroline M.</au><au>Provenzano, Frank A.</au><au>Sands, Tristan T.</au><au>Fee, Robert J.</au><au>Montes, Jacqueline</au><au>Shen, Yufeng</au><au>Chung, Wendy K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heterogeneity of comprehensive clinical phenotype and longitudinal adaptive function and correlation with computational predictions of severity of missense genotypes in KIF1A-associated neurological disorder</atitle><jtitle>Genetics in medicine</jtitle><addtitle>Genet Med</addtitle><date>2024-08</date><risdate>2024</risdate><volume>26</volume><issue>8</issue><spage>101169</spage><pages>101169-</pages><artnum>101169</artnum><issn>1098-3600</issn><issn>1530-0366</issn><eissn>1530-0366</eissn><abstract>Pathogenic variants in kinesin family member 1A (KIF1A) are associated with KIF1A-associated neurological disorder. We report the clinical phenotypes and correlate genotypes of individuals with KIF1A-associated neurological disorder.
Medical history and adaptive function were assessed longitudinally. In-person evaluations included neurological, motor, ophthalmologic, and cognitive assessments.
We collected online data on 177 individuals. Fifty-seven individuals were also assessed in-person. Most individuals had de novo heterozygous missense likely pathogenic/pathogenic KIF1A variants. The most common characteristics were hypotonia, spasticity, ataxia, seizures, optic nerve atrophy, cerebellar atrophy, and cognitive impairment. Mean Vineland adaptive behavior composite score (VABS-ABC) was low (M = 62.9, SD = 19.1). The mean change in VABS-ABC over time was −3.1 (SD = 7.3). The decline in VABS-ABC was associated with the age at first assessment and abnormal electroencephalogram/seizure. There was a positive correlation between evolutionary scale model (ESM) score for the variants and final VABS-ABC (P = .003). Abnormal electroencephalogram/seizure, neuroimaging result, and ESM explain 34% of the variance in final VABS-ABC (P < .001).
In-person assessment confirmed caregiver report and identified additional visual deficits. Adaptive function declined over time consistent with both the neurodevelopmental and neurodegenerative nature of the condition. Using ESM score assists in predicting phenotype across a wide range of unique variants.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38785164</pmid><doi>10.1016/j.gim.2024.101169</doi><orcidid>https://orcid.org/0000-0003-3438-5685</orcidid><orcidid>https://orcid.org/0000-0003-3576-5217</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1098-3600 |
ispartof | Genetics in medicine, 2024-08, Vol.26 (8), p.101169, Article 101169 |
issn | 1098-3600 1530-0366 1530-0366 |
language | eng |
recordid | cdi_proquest_miscellaneous_3060380365 |
source | MEDLINE; Alma/SFX Local Collection |
subjects | Adaptive function Adolescent Adult Child Child, Preschool Cognitive impairment Electroencephalography ESM Female Genotype Humans Infant KIF1A Kinesins - genetics Longitudinal Studies Male Middle Aged Mutation, Missense - genetics Nervous System Diseases - genetics Nervous System Diseases - pathology Nervous System Diseases - physiopathology Neurological disorder Phenotype Seizures - genetics Seizures - physiopathology Young Adult |
title | Heterogeneity of comprehensive clinical phenotype and longitudinal adaptive function and correlation with computational predictions of severity of missense genotypes in KIF1A-associated neurological disorder |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T03%3A13%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Heterogeneity%20of%20comprehensive%20clinical%20phenotype%20and%20longitudinal%20adaptive%20function%20and%20correlation%20with%20computational%20predictions%20of%20severity%20of%20missense%20genotypes%20in%20KIF1A-associated%20neurological%20disorder&rft.jtitle=Genetics%20in%20medicine&rft.au=Sudnawa,%20Khemika%20K.&rft.date=2024-08&rft.volume=26&rft.issue=8&rft.spage=101169&rft.pages=101169-&rft.artnum=101169&rft.issn=1098-3600&rft.eissn=1530-0366&rft_id=info:doi/10.1016/j.gim.2024.101169&rft_dat=%3Cproquest_cross%3E3060380365%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3060380365&rft_id=info:pmid/38785164&rft_els_id=S1098360024001035&rfr_iscdi=true |