Homozygous N-terminal missense variant in PLEKHG5 associated with intermediate CMT: A case report

Danique Beijer; Kiran Polavarapu; Veeramani Preethish-Kumar; Mainak Bardhan; Maike F. Dohrn; Adriana Rebelo; Stephan Züchner; Atchayaram Nalini

doi:10.3233/JND-210716

Homozygous N-terminal missense variant in PLEKHG5 associated with intermediate CMT: A case report

Danique Beijer, Kiran Polavarapu, Veeramani Preethish-Kumar, Mainak Bardhan, Maike F. Dohrn, Adriana Rebelo, Stephan Züchner, Atchayaram Nalini

Research output: Contribution to journal › Article › peer-review

Abstract

Mutations in PLEKHG5, a pleckstrin homology domain containing member of the GEF family, are associated with distal spinal muscular atrophy and intermediate Charcot-Marie-Tooth disease. Here, we describe an isolated case with distal intermediate neuropathy with scapular winging. By whole exome sequencing, we identified the homozygous PLEKHG5 Arg97Gln missense mutation, located in the N-terminal region of the protein. This mutation resides between a zinc-finger motif and a RBD domain, involved in binding rnd3, a RhoA effector protein. We conclude that based on the characteristic phenotype presented by the patient and the supportive genetic findings, the PLEKHG5 mutation is the causative variant.

Original language	English (US)
Pages (from-to)	347-351
Number of pages	5
Journal	Journal of neuromuscular diseases
Volume	9
Issue number	2
DOIs	https://doi.org/10.3233/JND-210716
State	Published - 2022
Externally published	Yes

Keywords

Charcot-Marie-Tooth disease
genetic diseases
high-throughput nucleotide sequencing
inborn
neurodegenerative diseases

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.3233/JND-210716

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Homozygous N-terminal missense variant in PLEKHG5 associated with intermediate CMT : A case report. / Beijer, Danique; Polavarapu, Kiran; Preethish-Kumar, Veeramani; Bardhan, Mainak; Dohrn, Maike F.; Rebelo, Adriana; Züchner, Stephan; Nalini, Atchayaram.

In: Journal of neuromuscular diseases, Vol. 9, No. 2, 2022, p. 347-351.

Research output: Contribution to journal › Article › peer-review

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abstract = "Mutations in PLEKHG5, a pleckstrin homology domain containing member of the GEF family, are associated with distal spinal muscular atrophy and intermediate Charcot-Marie-Tooth disease. Here, we describe an isolated case with distal intermediate neuropathy with scapular winging. By whole exome sequencing, we identified the homozygous PLEKHG5 Arg97Gln missense mutation, located in the N-terminal region of the protein. This mutation resides between a zinc-finger motif and a RBD domain, involved in binding rnd3, a RhoA effector protein. We conclude that based on the characteristic phenotype presented by the patient and the supportive genetic findings, the PLEKHG5 mutation is the causative variant. ",

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AU - Polavarapu, Kiran

AU - Preethish-Kumar, Veeramani

AU - Bardhan, Mainak

AU - Dohrn, Maike F.

AU - Rebelo, Adriana

AU - Züchner, Stephan

AU - Nalini, Atchayaram

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AB - Mutations in PLEKHG5, a pleckstrin homology domain containing member of the GEF family, are associated with distal spinal muscular atrophy and intermediate Charcot-Marie-Tooth disease. Here, we describe an isolated case with distal intermediate neuropathy with scapular winging. By whole exome sequencing, we identified the homozygous PLEKHG5 Arg97Gln missense mutation, located in the N-terminal region of the protein. This mutation resides between a zinc-finger motif and a RBD domain, involved in binding rnd3, a RhoA effector protein. We conclude that based on the characteristic phenotype presented by the patient and the supportive genetic findings, the PLEKHG5 mutation is the causative variant.

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Homozygous N-terminal missense variant in PLEKHG5 associated with intermediate CMT: A case report

Abstract

Keywords

ASJC Scopus subject areas

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