SHQ1-associated neurodevelopmental disorder: Report of the first homozygous variant in unrelated patients and review of the literature.

Aljouhra AlHargan; Mohammed A AlMuhaizea; Rawan AlMass; Ali H Alwadei; Maha Daghestani; Stefan T. Arold; Namik Kaya

doi:10.1038/s41439-023-00234-z

SHQ1-associated neurodevelopmental disorder: Report of the first homozygous variant in unrelated patients and review of the literature.

Aljouhra AlHargan, Mohammed A AlMuhaizea, Rawan AlMass, Ali H Alwadei, Maha Daghestani, Stefan T. Arold, Namik Kaya

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Abstract

Compound heterozygous mutations in SHQ1 have been associated with a rare and severe neurological disorder characterized by global developmental delay (GDD), cerebellar degeneration coupled with seizures, and early-onset dystonia. Currently, only five affected individuals have been documented in the literature. Here, we report three children from two unrelated families harboring a homozygous variant in the gene but with a milder phenotype than previously described. The patients had GDD and seizures. Magnetic resonance imaging analyses revealed diffuse white matter hypomyelination. Sanger sequencing confirmed the whole-exome sequencing results and revealed full segregation of the missense variant (SHQ1:c.833 T > C; p.I278T) in both families. We performed a comprehensive in silico analysis using different prediction classifiers and structural modeling of the variant. Our findings demonstrate that this novel homozygous variant in SHQ1 is likely to be pathogenic and leads to the clinical features observed in our patients.

Original language	English (US)
Journal	Human Genome Variation
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41439-023-00234-z
State	Published - Feb 22 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-02-27
Acknowledged KAUST grant number(s): REI/1/4446-01
Acknowledgements: Funds were received from the King Salman Center for Disability Research (RAC/ORA#2180004) (NK). STA was supported by the King Abdullah University of Science and Technology (KAUST) through the baseline fund and Award No. REI/1/4446-01 from the Office of Sponsored Research (OSR). We thank the families, the Center for Genomic Medicine Core Laboratories, the Research Advisory Council Committees, and the KFSHRC Purchasing Departments for facilitating and expediting our requests. We extend our special thanks to the King Salman Center for Disability Research (KSCDR; RAC/ORA#2180004, NK) for grant support during the study. For computer time, this research used the resources of the Supercomputing Laboratory at King Abdullah University of Science & Technology (KAUST) in Thuwal, Saudi Arabia.

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10.1038/s41439-023-00234-z

https://repository.kaust.edu.sa/bitstream/10754/688179/1/s41439-023-00234-z%20%281%29.pdf

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title = "SHQ1-associated neurodevelopmental disorder: Report of the first homozygous variant in unrelated patients and review of the literature.",

abstract = "Compound heterozygous mutations in SHQ1 have been associated with a rare and severe neurological disorder characterized by global developmental delay (GDD), cerebellar degeneration coupled with seizures, and early-onset dystonia. Currently, only five affected individuals have been documented in the literature. Here, we report three children from two unrelated families harboring a homozygous variant in the gene but with a milder phenotype than previously described. The patients had GDD and seizures. Magnetic resonance imaging analyses revealed diffuse white matter hypomyelination. Sanger sequencing confirmed the whole-exome sequencing results and revealed full segregation of the missense variant (SHQ1:c.833 T > C; p.I278T) in both families. We performed a comprehensive in silico analysis using different prediction classifiers and structural modeling of the variant. Our findings demonstrate that this novel homozygous variant in SHQ1 is likely to be pathogenic and leads to the clinical features observed in our patients.",

author = "Aljouhra AlHargan and AlMuhaizea, {Mohammed A} and Rawan AlMass and Alwadei, {Ali H} and Maha Daghestani and Arold, {Stefan T.} and Namik Kaya",

note = "KAUST Repository Item: Exported on 2023-02-27 Acknowledged KAUST grant number(s): REI/1/4446-01 Acknowledgements: Funds were received from the King Salman Center for Disability Research (RAC/ORA#2180004) (NK). STA was supported by the King Abdullah University of Science and Technology (KAUST) through the baseline fund and Award No. REI/1/4446-01 from the Office of Sponsored Research (OSR). We thank the families, the Center for Genomic Medicine Core Laboratories, the Research Advisory Council Committees, and the KFSHRC Purchasing Departments for facilitating and expediting our requests. We extend our special thanks to the King Salman Center for Disability Research (KSCDR; RAC/ORA#2180004, NK) for grant support during the study. For computer time, this research used the resources of the Supercomputing Laboratory at King Abdullah University of Science & Technology (KAUST) in Thuwal, Saudi Arabia.",

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doi = "10.1038/s41439-023-00234-z",

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AU - AlHargan, Aljouhra

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AU - AlMass, Rawan

AU - Alwadei, Ali H

AU - Daghestani, Maha

AU - Arold, Stefan T.

AU - Kaya, Namik

N1 - KAUST Repository Item: Exported on 2023-02-27 Acknowledged KAUST grant number(s): REI/1/4446-01 Acknowledgements: Funds were received from the King Salman Center for Disability Research (RAC/ORA#2180004) (NK). STA was supported by the King Abdullah University of Science and Technology (KAUST) through the baseline fund and Award No. REI/1/4446-01 from the Office of Sponsored Research (OSR). We thank the families, the Center for Genomic Medicine Core Laboratories, the Research Advisory Council Committees, and the KFSHRC Purchasing Departments for facilitating and expediting our requests. We extend our special thanks to the King Salman Center for Disability Research (KSCDR; RAC/ORA#2180004, NK) for grant support during the study. For computer time, this research used the resources of the Supercomputing Laboratory at King Abdullah University of Science & Technology (KAUST) in Thuwal, Saudi Arabia.

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N2 - Compound heterozygous mutations in SHQ1 have been associated with a rare and severe neurological disorder characterized by global developmental delay (GDD), cerebellar degeneration coupled with seizures, and early-onset dystonia. Currently, only five affected individuals have been documented in the literature. Here, we report three children from two unrelated families harboring a homozygous variant in the gene but with a milder phenotype than previously described. The patients had GDD and seizures. Magnetic resonance imaging analyses revealed diffuse white matter hypomyelination. Sanger sequencing confirmed the whole-exome sequencing results and revealed full segregation of the missense variant (SHQ1:c.833 T > C; p.I278T) in both families. We performed a comprehensive in silico analysis using different prediction classifiers and structural modeling of the variant. Our findings demonstrate that this novel homozygous variant in SHQ1 is likely to be pathogenic and leads to the clinical features observed in our patients.

AB - Compound heterozygous mutations in SHQ1 have been associated with a rare and severe neurological disorder characterized by global developmental delay (GDD), cerebellar degeneration coupled with seizures, and early-onset dystonia. Currently, only five affected individuals have been documented in the literature. Here, we report three children from two unrelated families harboring a homozygous variant in the gene but with a milder phenotype than previously described. The patients had GDD and seizures. Magnetic resonance imaging analyses revealed diffuse white matter hypomyelination. Sanger sequencing confirmed the whole-exome sequencing results and revealed full segregation of the missense variant (SHQ1:c.833 T > C; p.I278T) in both families. We performed a comprehensive in silico analysis using different prediction classifiers and structural modeling of the variant. Our findings demonstrate that this novel homozygous variant in SHQ1 is likely to be pathogenic and leads to the clinical features observed in our patients.

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UR - https://www.nature.com/articles/s41439-023-00234-z

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DO - 10.1038/s41439-023-00234-z

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JO - Human Genome Variation

JF - Human Genome Variation

IS - 1

ER -

SHQ1-associated neurodevelopmental disorder: Report of the first homozygous variant in unrelated patients and review of the literature.

Abstract

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