Homozygous variant, p.(Arg643Trp) in VAC14 causes striatonigral degeneration: report of a novel variant and review of VAC14-related disorders

Parneet Kaur, Gandham Sri Lakshmi Bhavani, Arun Raj, Katta Mohan Girisha, Anju Shukla

Research output: Contribution to journalArticle

Abstract

VAC14-related disorders include two distinct phenotypes, striatonigral degeneration [MIM# 617054] and Yunis–Varon syndrome. Striatonigral degeneration is a recently described childhood onset dystonia caused by pathogenic variants in VAC14. It is characterized by a period of apparent normalcy followed by abrupt onset neuroregression, dystonia, involuntary movements and degenerative brain lesions involving caudate nucleus, putamen and substantia nigra. Yunis–Varon syndrome is a well described severe condition characterised by skeletal findings and dysmorphism along with neuronal degeneration. Pathogenic variants in FIG4 have been previously reported to cause Yunis–Varon syndrome. Recently, loss of function variants in VAC14 were also reported in an individual affected with Yunis–Varon syndrome. Total seven individuals from four families are reported to have VAC14-related disorders till date. Here, we report another individual with clinical and radiological features suggestive of striatonigral degeneration with homozygous missense variant in VAC14. The patient fibroblasts showed extensive vacuolization, characteristic of VAC14-related disorders. We also review the phenotype and genotype associated with these disorders.

Original languageEnglish
Pages (from-to)1237-1242
Number of pages6
JournalJournal of Human Genetics
Volume64
Issue number12
DOIs
Publication statusPublished - 01-12-2019

Fingerprint

Striatonigral Degeneration
Dystonic Disorders
Phenotype
Dystonia
Caudate Nucleus
Putamen
Dyskinesias
Fibroblasts
Genotype
Brain

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

@article{4e9e9ee0705d4bdb9464d9c918b6f2d2,
title = "Homozygous variant, p.(Arg643Trp) in VAC14 causes striatonigral degeneration: report of a novel variant and review of VAC14-related disorders",
abstract = "VAC14-related disorders include two distinct phenotypes, striatonigral degeneration [MIM# 617054] and Yunis–Varon syndrome. Striatonigral degeneration is a recently described childhood onset dystonia caused by pathogenic variants in VAC14. It is characterized by a period of apparent normalcy followed by abrupt onset neuroregression, dystonia, involuntary movements and degenerative brain lesions involving caudate nucleus, putamen and substantia nigra. Yunis–Varon syndrome is a well described severe condition characterised by skeletal findings and dysmorphism along with neuronal degeneration. Pathogenic variants in FIG4 have been previously reported to cause Yunis–Varon syndrome. Recently, loss of function variants in VAC14 were also reported in an individual affected with Yunis–Varon syndrome. Total seven individuals from four families are reported to have VAC14-related disorders till date. Here, we report another individual with clinical and radiological features suggestive of striatonigral degeneration with homozygous missense variant in VAC14. The patient fibroblasts showed extensive vacuolization, characteristic of VAC14-related disorders. We also review the phenotype and genotype associated with these disorders.",
author = "Parneet Kaur and Bhavani, {Gandham Sri Lakshmi} and Arun Raj and Girisha, {Katta Mohan} and Anju Shukla",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s10038-019-0678-1",
language = "English",
volume = "64",
pages = "1237--1242",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Nature Publishing Group",
number = "12",

}

Homozygous variant, p.(Arg643Trp) in VAC14 causes striatonigral degeneration : report of a novel variant and review of VAC14-related disorders. / Kaur, Parneet; Bhavani, Gandham Sri Lakshmi; Raj, Arun; Girisha, Katta Mohan; Shukla, Anju.

In: Journal of Human Genetics, Vol. 64, No. 12, 01.12.2019, p. 1237-1242.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Homozygous variant, p.(Arg643Trp) in VAC14 causes striatonigral degeneration

T2 - report of a novel variant and review of VAC14-related disorders

AU - Kaur, Parneet

AU - Bhavani, Gandham Sri Lakshmi

AU - Raj, Arun

AU - Girisha, Katta Mohan

AU - Shukla, Anju

PY - 2019/12/1

Y1 - 2019/12/1

N2 - VAC14-related disorders include two distinct phenotypes, striatonigral degeneration [MIM# 617054] and Yunis–Varon syndrome. Striatonigral degeneration is a recently described childhood onset dystonia caused by pathogenic variants in VAC14. It is characterized by a period of apparent normalcy followed by abrupt onset neuroregression, dystonia, involuntary movements and degenerative brain lesions involving caudate nucleus, putamen and substantia nigra. Yunis–Varon syndrome is a well described severe condition characterised by skeletal findings and dysmorphism along with neuronal degeneration. Pathogenic variants in FIG4 have been previously reported to cause Yunis–Varon syndrome. Recently, loss of function variants in VAC14 were also reported in an individual affected with Yunis–Varon syndrome. Total seven individuals from four families are reported to have VAC14-related disorders till date. Here, we report another individual with clinical and radiological features suggestive of striatonigral degeneration with homozygous missense variant in VAC14. The patient fibroblasts showed extensive vacuolization, characteristic of VAC14-related disorders. We also review the phenotype and genotype associated with these disorders.

AB - VAC14-related disorders include two distinct phenotypes, striatonigral degeneration [MIM# 617054] and Yunis–Varon syndrome. Striatonigral degeneration is a recently described childhood onset dystonia caused by pathogenic variants in VAC14. It is characterized by a period of apparent normalcy followed by abrupt onset neuroregression, dystonia, involuntary movements and degenerative brain lesions involving caudate nucleus, putamen and substantia nigra. Yunis–Varon syndrome is a well described severe condition characterised by skeletal findings and dysmorphism along with neuronal degeneration. Pathogenic variants in FIG4 have been previously reported to cause Yunis–Varon syndrome. Recently, loss of function variants in VAC14 were also reported in an individual affected with Yunis–Varon syndrome. Total seven individuals from four families are reported to have VAC14-related disorders till date. Here, we report another individual with clinical and radiological features suggestive of striatonigral degeneration with homozygous missense variant in VAC14. The patient fibroblasts showed extensive vacuolization, characteristic of VAC14-related disorders. We also review the phenotype and genotype associated with these disorders.

UR - http://www.scopus.com/inward/record.url?scp=85074193595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074193595&partnerID=8YFLogxK

U2 - 10.1038/s10038-019-0678-1

DO - 10.1038/s10038-019-0678-1

M3 - Article

C2 - 31591492

AN - SCOPUS:85074193595

VL - 64

SP - 1237

EP - 1242

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 12

ER -