Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling
Purpose - Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
18 August 2022
|
| In: |
Genetics in medicine
Year: 2022, Jahrgang: 24, Heft: 10, Pages: 2065-2078 |
| ISSN: | 1530-0366 |
| DOI: | 10.1016/j.gim.2022.07.005 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.gim.2022.07.005 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1098360022008425 
|
| Verfasserangaben: | Alexander M. Holtz, Rachel VanCoillie, Elizabeth A. Vansickle, Deanna Alexis Carere, Kara Withrow, Erin Torti, Jane Juusola, Francisca Millan, Richard Person, Maria J. Guillen Sacoto, Yue Si, Ingrid M. Wentzensen, Jada Pugh, Georgia Vasileiou, Melissa Rieger, André Reis, Emanuela Argilli, Elliott H. Sherr, Kimberly A. Aldinger, William B. Dobyns, Theresa Brunet, Julia Hoefele, Matias Wagner, Benjamin Haber, Urania Kotzaeridou, Boris Keren, Delphine Heron, Cyril Mignot, Solveig Heide, Thomas Courtin, Julien Buratti, Serini Murugasen, Kirsten A. Donald, Emily O’Heir, Shade Moody, Katherine H. Kim, Barbara K. Burton, Grace Yoon, Miguel del Campo, Diane Masser-Frye, Mariya Kozenko, Christina Parkinson, Susan L. Sell, Patricia L. Gordon, Jeremy W. Prokop, Amel Karaa, Caleb Bupp, Benjamin A. Raby |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1834607523 | ||
| 003 | DE-627 | ||
| 005 | 20230706233607.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230213s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.gim.2022.07.005 |2 doi | |
| 035 | |a (DE-627)1834607523 | ||
| 035 | |a (DE-599)KXP1834607523 | ||
| 035 | |a (OCoLC)1389535636 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Holtz, Alexander M. |e VerfasserIn |0 (DE-588)1280833122 |0 (DE-627)1834609992 |4 aut | |
| 245 | 1 | 0 | |a Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling |c Alexander M. Holtz, Rachel VanCoillie, Elizabeth A. Vansickle, Deanna Alexis Carere, Kara Withrow, Erin Torti, Jane Juusola, Francisca Millan, Richard Person, Maria J. Guillen Sacoto, Yue Si, Ingrid M. Wentzensen, Jada Pugh, Georgia Vasileiou, Melissa Rieger, André Reis, Emanuela Argilli, Elliott H. Sherr, Kimberly A. Aldinger, William B. Dobyns, Theresa Brunet, Julia Hoefele, Matias Wagner, Benjamin Haber, Urania Kotzaeridou, Boris Keren, Delphine Heron, Cyril Mignot, Solveig Heide, Thomas Courtin, Julien Buratti, Serini Murugasen, Kirsten A. Donald, Emily O’Heir, Shade Moody, Katherine H. Kim, Barbara K. Burton, Grace Yoon, Miguel del Campo, Diane Masser-Frye, Mariya Kozenko, Christina Parkinson, Susan L. Sell, Patricia L. Gordon, Jeremy W. Prokop, Amel Karaa, Caleb Bupp, Benjamin A. Raby |
| 264 | 1 | |c 18 August 2022 | |
| 300 | |a 14 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 13.02.2023 | ||
| 520 | |a Purpose - Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10. - Methods - An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis. - Results - We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a broad spectrum of neurodevelopmental disorders and variable congenital anomalies that affect most organ systems and were recapitulated in animal models of altered MYH10 activity. Variants were typically de novo missense changes with clustering observed in the motor domain. MYH10 knockout cells showed defects in primary ciliogenesis and reduced ciliary length with impaired Hedgehog signaling. MYH10 variant overexpression produced a dominant-negative effect on ciliary length. - Conclusion - These data presented a novel genetic cause of isolated and syndromic neurodevelopmental disorders related to heterozygous variants in the MYH10 gene with implications for disrupted primary cilia length control and altered Hedgehog signaling in disease pathogenesis. | ||
| 650 | 4 | |a Hedgehog signaling | |
| 650 | 4 | |a MYH10 | |
| 650 | 4 | |a Neurodevelopmental disorder | |
| 650 | 4 | |a Nonmuscle myosin | |
| 650 | 4 | |a Primary cilia | |
| 700 | 1 | |a VanCoillie, Rachel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vansickle, Elizabeth A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Carere, Deanna Alexis |e VerfasserIn |4 aut | |
| 700 | 1 | |a Withrow, Kara |e VerfasserIn |4 aut | |
| 700 | 1 | |a Torti, Erin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Juusola, Jane |e VerfasserIn |4 aut | |
| 700 | 1 | |a Millan, Francisca |e VerfasserIn |4 aut | |
| 700 | 1 | |a Person, Richard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Guillen Sacoto, Maria J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Si, Yue |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wentzensen, Ingrid M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pugh, Jada |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vasileiou, Georgia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rieger, Melissa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Reis, André |e VerfasserIn |4 aut | |
| 700 | 1 | |a Argilli, Emanuela |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sherr, Elliott H. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Aldinger, Kimberly A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dobyns, William B. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brunet, Theresa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hoefele, Julia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wagner, Matias |e VerfasserIn |4 aut | |
| 700 | 1 | |a Haber, Benjamin |d 1984- |e VerfasserIn |0 (DE-588)1078266212 |0 (DE-627)838220843 |0 (DE-576)450442101 |4 aut | |
| 700 | 1 | |a Kotzaeridou, Urania |e VerfasserIn |0 (DE-588)1070020834 |0 (DE-627)823189996 |0 (DE-576)429699948 |4 aut | |
| 700 | 1 | |a Keren, Boris |e VerfasserIn |4 aut | |
| 700 | 1 | |a Heron, Delphine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mignot, Cyril |e VerfasserIn |4 aut | |
| 700 | 1 | |a Heide, Solveig |e VerfasserIn |4 aut | |
| 700 | 1 | |a Courtin, Thomas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Buratti, Julien |e VerfasserIn |4 aut | |
| 700 | 1 | |a Murugasen, Serini |e VerfasserIn |4 aut | |
| 700 | 1 | |a Donald, Kirsten A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a O’Heir, Emily |e VerfasserIn |4 aut | |
| 700 | 1 | |a Moody, Shade |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kim, Katherine H. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Burton, Barbara K. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yoon, Grace |e VerfasserIn |4 aut | |
| 700 | 1 | |a Campo, Miguel del |e VerfasserIn |4 aut | |
| 700 | 1 | |a Masser-Frye, Diane |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kozenko, Mariya |e VerfasserIn |4 aut | |
| 700 | 1 | |a Parkinson, Christina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sell, Susan L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gordon, Patricia L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Prokop, Jeremy W. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Karaa, Amel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bupp, Caleb |e VerfasserIn |4 aut | |
| 700 | 1 | |a Raby, Benjamin A. |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Genetics in medicine |d Amsterdam : Elsevier, 1998 |g 24(2022), 10 vom: Okt., Seite 2065-2078 |h Online-Ressource |w (DE-627)338073361 |w (DE-600)2063504-7 |w (DE-576)109132475 |x 1530-0366 |7 nnas |a Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling |
| 773 | 1 | 8 | |g volume:24 |g year:2022 |g number:10 |g month:10 |g pages:2065-2078 |g extent:14 |a Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.gim.2022.07.005 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S1098360022008425 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230213 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 1070020834 |a Kotzaeridou, Urania |m 1070020834:Kotzaeridou, Urania |d 910000 |d 910500 |d 50000 |e 910000PK1070020834 |e 910500PK1070020834 |e 50000PK1070020834 |k 0/910000/ |k 1/910000/910500/ |k 0/50000/ |p 25 | ||
| 998 | |g 1078266212 |a Haber, Benjamin |m 1078266212:Haber, Benjamin |d 50000 |e 50000PH1078266212 |k 0/50000/ |p 24 | ||
| 999 | |a KXP-PPN1834607523 |e 4271190926 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"recId":"1834607523","language":["eng"],"name":{"displayForm":["Alexander M. Holtz, Rachel VanCoillie, Elizabeth A. Vansickle, Deanna Alexis Carere, Kara Withrow, Erin Torti, Jane Juusola, Francisca Millan, Richard Person, Maria J. Guillen Sacoto, Yue Si, Ingrid M. Wentzensen, Jada Pugh, Georgia Vasileiou, Melissa Rieger, André Reis, Emanuela Argilli, Elliott H. Sherr, Kimberly A. Aldinger, William B. Dobyns, Theresa Brunet, Julia Hoefele, Matias Wagner, Benjamin Haber, Urania Kotzaeridou, Boris Keren, Delphine Heron, Cyril Mignot, Solveig Heide, Thomas Courtin, Julien Buratti, Serini Murugasen, Kirsten A. Donald, Emily O’Heir, Shade Moody, Katherine H. Kim, Barbara K. Burton, Grace Yoon, Miguel del Campo, Diane Masser-Frye, Mariya Kozenko, Christina Parkinson, Susan L. Sell, Patricia L. Gordon, Jeremy W. Prokop, Amel Karaa, Caleb Bupp, Benjamin A. Raby"]},"relHost":[{"disp":"Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signalingGenetics in medicine","type":{"media":"Online-Ressource","bibl":"periodical"},"physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["1530-0366"],"eki":["338073361"],"zdb":["2063504-7"]},"note":["Gesehen am 27.07.2023"],"recId":"338073361","corporate":[{"role":"isb","roleDisplay":"Herausgebendes Organ","display":"American College of Medical Genetics"}],"origin":[{"dateIssuedDisp":"1998-","publisher":"Elsevier ; Springer Nature ; Lippincott, Williams & Wilkins","publisherPlace":"Amsterdam ; London, UK ; Baltimore, Md.","dateIssuedKey":"1998"}],"title":[{"title_sort":"Genetics in medicine","title":"Genetics in medicine","subtitle":"official journal of the American College of Medical Genetics"}],"titleAlt":[{"title":"GIM"}],"pubHistory":["1.1998/99 -"],"part":{"text":"24(2022), 10 vom: Okt., Seite 2065-2078","pages":"2065-2078","issue":"10","extent":"14","volume":"24","year":"2022"},"language":["eng"]}],"id":{"doi":["10.1016/j.gim.2022.07.005"],"eki":["1834607523"]},"note":["Gesehen am 13.02.2023"],"person":[{"role":"aut","given":"Alexander M.","roleDisplay":"VerfasserIn","family":"Holtz","display":"Holtz, Alexander M."},{"family":"VanCoillie","display":"VanCoillie, Rachel","roleDisplay":"VerfasserIn","given":"Rachel","role":"aut"},{"display":"Vansickle, Elizabeth A.","family":"Vansickle","role":"aut","roleDisplay":"VerfasserIn","given":"Elizabeth A."},{"roleDisplay":"VerfasserIn","given":"Deanna Alexis","role":"aut","family":"Carere","display":"Carere, Deanna Alexis"},{"given":"Kara","roleDisplay":"VerfasserIn","role":"aut","family":"Withrow","display":"Withrow, Kara"},{"roleDisplay":"VerfasserIn","given":"Erin","role":"aut","display":"Torti, Erin","family":"Torti"},{"family":"Juusola","display":"Juusola, Jane","given":"Jane","roleDisplay":"VerfasserIn","role":"aut"},{"display":"Millan, Francisca","family":"Millan","given":"Francisca","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Person","display":"Person, Richard","roleDisplay":"VerfasserIn","given":"Richard","role":"aut"},{"family":"Guillen Sacoto","display":"Guillen Sacoto, Maria J.","roleDisplay":"VerfasserIn","given":"Maria J.","role":"aut"},{"given":"Yue","roleDisplay":"VerfasserIn","role":"aut","family":"Si","display":"Si, Yue"},{"display":"Wentzensen, Ingrid M.","family":"Wentzensen","role":"aut","roleDisplay":"VerfasserIn","given":"Ingrid M."},{"given":"Jada","roleDisplay":"VerfasserIn","role":"aut","display":"Pugh, Jada","family":"Pugh"},{"role":"aut","roleDisplay":"VerfasserIn","given":"Georgia","family":"Vasileiou","display":"Vasileiou, Georgia"},{"role":"aut","given":"Melissa","roleDisplay":"VerfasserIn","family":"Rieger","display":"Rieger, Melissa"},{"given":"André","roleDisplay":"VerfasserIn","role":"aut","family":"Reis","display":"Reis, André"},{"given":"Emanuela","roleDisplay":"VerfasserIn","role":"aut","family":"Argilli","display":"Argilli, Emanuela"},{"role":"aut","roleDisplay":"VerfasserIn","given":"Elliott H.","family":"Sherr","display":"Sherr, Elliott H."},{"given":"Kimberly A.","roleDisplay":"VerfasserIn","role":"aut","display":"Aldinger, Kimberly A.","family":"Aldinger"},{"given":"William B.","roleDisplay":"VerfasserIn","role":"aut","family":"Dobyns","display":"Dobyns, William B."},{"given":"Theresa","roleDisplay":"VerfasserIn","role":"aut","display":"Brunet, Theresa","family":"Brunet"},{"display":"Hoefele, Julia","family":"Hoefele","role":"aut","roleDisplay":"VerfasserIn","given":"Julia"},{"role":"aut","roleDisplay":"VerfasserIn","given":"Matias","display":"Wagner, Matias","family":"Wagner"},{"display":"Haber, Benjamin","family":"Haber","role":"aut","roleDisplay":"VerfasserIn","given":"Benjamin"},{"display":"Kotzaeridou, Urania","family":"Kotzaeridou","given":"Urania","roleDisplay":"VerfasserIn","role":"aut"},{"role":"aut","roleDisplay":"VerfasserIn","given":"Boris","display":"Keren, Boris","family":"Keren"},{"display":"Heron, Delphine","family":"Heron","role":"aut","given":"Delphine","roleDisplay":"VerfasserIn"},{"role":"aut","given":"Cyril","roleDisplay":"VerfasserIn","display":"Mignot, Cyril","family":"Mignot"},{"display":"Heide, Solveig","family":"Heide","role":"aut","given":"Solveig","roleDisplay":"VerfasserIn"},{"role":"aut","given":"Thomas","roleDisplay":"VerfasserIn","display":"Courtin, Thomas","family":"Courtin"},{"roleDisplay":"VerfasserIn","given":"Julien","role":"aut","display":"Buratti, Julien","family":"Buratti"},{"role":"aut","given":"Serini","roleDisplay":"VerfasserIn","family":"Murugasen","display":"Murugasen, Serini"},{"display":"Donald, Kirsten A.","family":"Donald","role":"aut","given":"Kirsten A.","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","given":"Emily","role":"aut","display":"O’Heir, Emily","family":"O’Heir"},{"role":"aut","given":"Shade","roleDisplay":"VerfasserIn","display":"Moody, Shade","family":"Moody"},{"roleDisplay":"VerfasserIn","given":"Katherine H.","role":"aut","display":"Kim, Katherine H.","family":"Kim"},{"family":"Burton","display":"Burton, Barbara K.","given":"Barbara K.","roleDisplay":"VerfasserIn","role":"aut"},{"display":"Yoon, Grace","family":"Yoon","role":"aut","given":"Grace","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","given":"Miguel del","role":"aut","display":"Campo, Miguel del","family":"Campo"},{"roleDisplay":"VerfasserIn","given":"Diane","role":"aut","family":"Masser-Frye","display":"Masser-Frye, Diane"},{"display":"Kozenko, Mariya","family":"Kozenko","role":"aut","roleDisplay":"VerfasserIn","given":"Mariya"},{"given":"Christina","roleDisplay":"VerfasserIn","role":"aut","family":"Parkinson","display":"Parkinson, Christina"},{"display":"Sell, Susan L.","family":"Sell","roleDisplay":"VerfasserIn","given":"Susan L.","role":"aut"},{"display":"Gordon, Patricia L.","family":"Gordon","role":"aut","given":"Patricia L.","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","given":"Jeremy W.","role":"aut","display":"Prokop, Jeremy W.","family":"Prokop"},{"family":"Karaa","display":"Karaa, Amel","role":"aut","roleDisplay":"VerfasserIn","given":"Amel"},{"display":"Bupp, Caleb","family":"Bupp","role":"aut","given":"Caleb","roleDisplay":"VerfasserIn"},{"role":"aut","roleDisplay":"VerfasserIn","given":"Benjamin A.","family":"Raby","display":"Raby, Benjamin A."}],"physDesc":[{"extent":"14 S."}],"title":[{"title_sort":"Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling","title":"Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling"}],"origin":[{"dateIssuedKey":"2022","dateIssuedDisp":"18 August 2022"}],"type":{"media":"Online-Ressource","bibl":"article-journal"}} | ||
| SRT | |a HOLTZALEXAHETEROZYGO1820 | ||