A Cockayne-like phenotype resulting from a de novo variant in MORC2: expanding the phenotype of MORC2-related disorders

Amytice Mirchi^{1

2

3}, Alexa Derksen^{1

3}, Luan T Tran^{1

3}, Isabelle De Bie^{4

5

6}, Amélie Nadeau⁷, Audrey Lovett^{2

8}, Anja Raams⁹, Wim Vermeulen⁹, Arjan F Theil⁹, Geneviève Bernard^{10

11

12

13

14}

Affiliations

¹ Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
² Department of Pediatrics, McGill University, Montreal, Canada.
³ Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, Canada.
⁴ Department of Human Genetics, McGill University, Montreal, Canada.
⁵ Department of Specialized Medicine, Division of Medical Genetics, McGill University, Montreal, Canada.
⁶ Department of Laboratory Medicine, McGill University Health Centre, Montreal, Canada.
⁷ Department of Pediatrics, Division of Pediatric Neurology, Université de Sherbrooke, Sherbrooke, QC, Canada.
⁸ Department of Dermatology, McGill University, Montreal, Canada.
⁹ Department of Molecular Genetics, Oncode Institute, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
¹⁰ Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. genevieve.bernard@mcgill.ca.
¹¹ Department of Pediatrics, McGill University, Montreal, Canada. genevieve.bernard@mcgill.ca.
¹² Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, Canada. genevieve.bernard@mcgill.ca.
¹³ Department of Human Genetics, McGill University, Montreal, Canada. genevieve.bernard@mcgill.ca.
¹⁴ Department of Specialized Medicine, Division of Medical Genetics, McGill University, Montreal, Canada. genevieve.bernard@mcgill.ca.

PMID: 35920923
DOI: 10.1007/s10048-022-00697-2

A Cockayne-like phenotype resulting from a de novo variant in MORC2: expanding the phenotype of MORC2-related disorders

Amytice Mirchi et al. Neurogenetics. 2022 Oct.

. 2022 Oct;23(4):271-274.

doi: 10.1007/s10048-022-00697-2. Epub 2022 Aug 3.

Authors

Affiliations

¹ Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
² Department of Pediatrics, McGill University, Montreal, Canada.
³ Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, Canada.
⁴ Department of Human Genetics, McGill University, Montreal, Canada.
⁵ Department of Specialized Medicine, Division of Medical Genetics, McGill University, Montreal, Canada.
⁶ Department of Laboratory Medicine, McGill University Health Centre, Montreal, Canada.
⁷ Department of Pediatrics, Division of Pediatric Neurology, Université de Sherbrooke, Sherbrooke, QC, Canada.
⁸ Department of Dermatology, McGill University, Montreal, Canada.
⁹ Department of Molecular Genetics, Oncode Institute, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
¹⁰ Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. genevieve.bernard@mcgill.ca.
¹¹ Department of Pediatrics, McGill University, Montreal, Canada. genevieve.bernard@mcgill.ca.
¹² Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, Canada. genevieve.bernard@mcgill.ca.
¹³ Department of Human Genetics, McGill University, Montreal, Canada. genevieve.bernard@mcgill.ca.
¹⁴ Department of Specialized Medicine, Division of Medical Genetics, McGill University, Montreal, Canada. genevieve.bernard@mcgill.ca.

PMID: 35920923
DOI: 10.1007/s10048-022-00697-2

Abstract

Cockayne syndrome is a rare inherited DNA repair multisystemic disorder. Here, we aim to raise awareness of the phenotypic resemblances between Cockayne syndrome and the neurodevelopmental disorder caused by pathogenic variants in MORC2, a gene also involved in DNA repair. Using exome sequencing, we identified a de novo pathogenic variant in MORC2 in our patient. Our patient's phenotype was characterized by multiple features evocative of Cockayne syndrome. Based on our patient's phenotype, in addition to the phenotypic description of patients with pathogenic variants in MORC2 reported in the literature, we suggest that pathogenic variants in this gene are associated with a Cockayne-like phenotype.

Keywords: Cockayne syndrome; Exome sequencing; MORC2; Neurodevelopmental disorder.

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References

1. Tchasovnikarova IA, Timms RT, Douse CH et al (2017) Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2. Nat Genet 49(7):1035–1044 - DOI - PubMed - PMC
1. Sevilla T, Lupo V, Martinez-Rubio D et al (2016) Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease. Brain 139(Pt 1):62–72 - DOI - PubMed
1. Schottmann G, Wagner C, Seifert F et al (2016) MORC2 mutation causes severe spinal muscular atrophy-phenotype, cerebellar atrophy, and diaphragmatic paralysis. Brain 139(Pt 12):e70 - DOI - PubMed
1. Guillen Sacoto MJ, Tchasovnikarova IA, Torti E et al (2020) De novo variants in the ATPase module of MORC2 cause a neurodevelopmental disorder with growth retardation and variable craniofacial dysmorphism. Am J Hum Genet 107(2):352–363 - DOI - PubMed - PMC
1. Theil AF, Botta E, Raams A et al (2019) Bi-allelic TARS mutations are associated with brittle hair phenotype. Am J Hum Genet 105(2):434–440 - DOI - PubMed - PMC

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A Cockayne-like phenotype resulting from a de novo variant in MORC2: expanding the phenotype of MORC2-related disorders

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A Cockayne-like phenotype resulting from a de novo variant in MORC2: expanding the phenotype of MORC2-related disorders

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