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Pathogenic Variants in ABHD16A Cause a Novel Psychomotor Developmental Disorder With Spastic Paraplegia.
Yahia, Ashraf; Elsayed, Liena E O; Valter, Remi; Hamed, Ahlam A A; Mohammed, Inaam N; Elseed, Maha A; Salih, Mustafa A; Esteves, Typhaine; Auger, Nicolas; Abubaker, Rayan; Koko, Mahmoud; Abozar, Fatima; Malik, Hiba; Adil, Rawaa; Emad, Sara; Musallam, Mhammed Alhassan; Idris, Razaz; Eltazi, Isra Z M; Babai, Arwa; Ahmed, Elhami A A; Abd Allah, Amal S I; Mairey, Mathilde; Ahmed, Ahmed K M A; Elbashir, Mustafa I; Brice, Alexis; Ibrahim, Muntaser E; Ahmed, Ammar E; Lamari, Foudil; Stevanin, Giovanni.
Afiliación
  • Yahia A; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Elsayed LEO; Department of Biochemistry, Faculty of Medicine, National University, Khartoum, Sudan.
  • Valter R; Sorbonne Université, Institut du Cerveau-Paris Brain Institute, INSERM, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.
  • Hamed AAA; Ecole Pratique des Hautes Etudes, EPHE, PSL Research University, Paris, France.
  • Mohammed IN; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Elseed MA; College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
  • Salih MA; Sorbonne Université, Institut du Cerveau-Paris Brain Institute, INSERM, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.
  • Esteves T; Ecole Pratique des Hautes Etudes, EPHE, PSL Research University, Paris, France.
  • Auger N; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Abubaker R; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Koko M; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Abozar F; Division of Pediatric Neurology, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • Malik H; Sorbonne Université, Institut du Cerveau-Paris Brain Institute, INSERM, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.
  • Adil R; Ecole Pratique des Hautes Etudes, EPHE, PSL Research University, Paris, France.
  • Emad S; Sorbonne Université, Institut du Cerveau-Paris Brain Institute, INSERM, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.
  • Musallam MA; Ecole Pratique des Hautes Etudes, EPHE, PSL Research University, Paris, France.
  • Idris R; Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
  • Eltazi IZM; Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, Tubingen, Germany.
  • Babai A; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Ahmed EAA; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Abd Allah ASI; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Mairey M; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Ahmed AKMA; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Elbashir MI; Letterkenny University Hospital, Letterkenny, Ireland.
  • Brice A; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Ibrahim ME; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Ahmed AE; UNESCO Chair on Bioethics, University of Khartoum, Khartoum, Sudan.
  • Lamari F; Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
  • Stevanin G; Sorbonne Université, Institut du Cerveau-Paris Brain Institute, INSERM, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.
Front Neurol ; 12: 720201, 2021.
Article en En | MEDLINE | ID: mdl-34489854
ABSTRACT

Introduction:

Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurological entity that includes more than 80 disorders which share lower limb spasticity as a common feature. Abnormalities in multiple cellular processes are implicated in their pathogenesis, including lipid metabolism; but still 40% of the patients are undiagnosed. Our goal was to identify the disease-causing variants in Sudanese families excluded for known genetic causes and describe a novel clinico-genetic entity.

Methods:

We studied four patients from two unrelated consanguineous Sudanese families who manifested a neurological phenotype characterized by spasticity, psychomotor developmental delay and/or regression, and intellectual impairment. We applied next-generation sequencing, bioinformatics analysis, and Sanger sequencing to identify the genetic culprit. We then explored the consequences of the identified variants in patients-derived fibroblasts using targeted-lipidomics strategies. Results and

Discussion:

Two homozygous variants in ABHD16A segregated with the disease in the two studied families. ABHD16A encodes the main brain phosphatidylserine hydrolase. In vitro, we confirmed that ABHD16A loss of function reduces the levels of certain long-chain lysophosphatidylserine species while increases the levels of multiple phosphatidylserine species in patient's fibroblasts.

Conclusion:

ABHD16A loss of function is implicated in the pathogenesis of a novel form of complex hereditary spastic paraplegia.
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Neurol Año: 2021 Tipo del documento: Article País de afiliación: Sudán

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Neurol Año: 2021 Tipo del documento: Article País de afiliación: Sudán
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