<scp>SCYL2</scp> ‐related autosomal recessive neurodevelopmental disorders: Arthrogryposis multiplex congenita‐4 and beyond?

SCY1-like protein 2 (SCYL2) is a member of the SCY1-like pseudokinase family which regulates secretory protein trafficking. It plays a crucial role in the nervous system by suppressing excitotoxicity in the developing brain. Scyl2 knockout mice have excess prenatal mortality and survivors show severe neurological dysfunction. Bi-allelic loss-of-function (LOF) variants in SCYL2 were recently associated with arthrogryposis multiplex congenita-4 (AMC4) following the report of 6 individuals from two consanguineous unrelated families. The AMC4 phenotype described included severe arthrogryposis, corpus callosum agenesis, epilepsy and frequently, early death. We describe here two additional similarly affected individuals with AMC4, including one diagnosed in the prenatal period, with bi-allelic LOF variants in SCYL2, and two individuals homozygous for missense variants in the protein kinase domain of SCYL2 and presenting with developmental delay only. Our study confirms the association of SCYL2 with AMC4 and suggests a milder phenotype can occur, extending the phenotypic spectrum of autosomal recessive SCYL2-related disorders.

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Journal
Clinical Genetics
Published
2024-08-21
DOI
https://doi.org/10.1111/cge.14608
Citations
1
Primary Topic
Genetics and Neurodevelopmental Disorders
Type
article
Field-Weighted Citation Impact
0.55

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article

SCYL2 ‐related autosomal recessive neurodevelopmental disorders: Arthrogryposis multiplex congenita‐4 and beyond?

Christel Thauvin‐Robinet, Frédéric Tran Mau‐Them, Rhonda E. Schnur, Laurence Olivier Faivre et al.
1 citations
Clinical Genetics
Genetics and Neurodevelopmental Disorders
0.55
article

SCYL2 ‐related autosomal recessive neurodevelopmental disorders: Arthrogryposis multiplex congenita‐4 and beyond?

Christel Thauvin‐Robinet, Frédéric Tran Mau‐Them, Rhonda E. Schnur, Laurence Olivier Faivre, Aurélien Juven, Hana Safraou, M. Brasseur‐Daudruy, Ajit Gandhi, Anne‐Claire Bréhin, Harsh Sheth, Ange‐Line Bruel, Faye L. Shapiro, Gabriella Vera, Marlène Malbos, Kristin G. Monaghan, Yannis Duffourd, Christophe Philippe, Florent Marguet, Amber Begtrup, Jayesh Sheth, Paul J. Benke
article en
1 citations

Abstract

SCY1-like protein 2 (SCYL2) is a member of the SCY1-like pseudokinase family which regulates secretory protein trafficking. It plays a crucial role in the nervous system by suppressing excitotoxicity in the developing brain. Scyl2 knockout mice have excess prenatal mortality and survivors show severe neurological dysfunction. Bi-allelic loss-of-function (LOF) variants in SCYL2 were recently associated with arthrogryposis multiplex congenita-4 (AMC4) following the report of 6 individuals from two consanguineous unrelated families. The AMC4 phenotype described included severe arthrogryposis, corpus callosum agenesis, epilepsy and frequently, early death. We describe here two additional similarly affected individuals with AMC4, including one diagnosed in the prenatal period, with bi-allelic LOF variants in SCYL2, and two individuals homozygous for missense variants in the protein kinase domain of SCYL2 and presenting with developmental delay only. Our study confirms the association of SCYL2 with AMC4 and suggests a milder phenotype can occur, extending the phenotypic spectrum of autosomal recessive SCYL2-related disorders.

Clinical GeneticsVol. 106(6)
Inserm (FR), Université de Bourgogne (FR), Cooper Medical School of Rowan University (US), Centre For Human Genetics (IN), Normandie Université (FR), Centre Hospitalier Régional de Metz-Thionville (FR), Université Bourgogne Franche-Comté (FR), Centre Hospitalier Universitaire de Rouen (FR), Cooper University Health Care (US), Joe DiMaggio Children's Hospital (US), Université de Rouen Normandie (FR)
European Commission
Good health and well-being
Openalex Percentile: Top 27%
Genetics and Neurodevelopmental Disorders
0.55
DOIOpen Access PDFOpenAlex
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