SGCE mutations cause psychiatric disorders: clinical and genetic characterization

Kathryn J. Peall; Daniel J. Smith; Manju A. Kurian; Mark Wardle; Adrian J. Waite; Tamasine Hedderly; Jean-Pierre Lin; Martin Smith; Alan Whone; Hardev Pall; Cathy White; Andrew Lux; Philip Jardine; Narinder Bajaj; Bryan Lynch; George Kirov; Sean O'Riordan; Michael Samuel; Timothy Lynch; Mary D. King; Patrick F. Chinnery; Thomas T. Warner; Derek J. Blake; Michael J. Owen; Huw R. Morris

doi:10.1093/brain/aws308

SGCE mutations cause psychiatric disorders: clinical and genetic characterization

Kathryn J. Peall^*, Daniel J. Smith, Manju A. Kurian, Mark Wardle, Adrian J. Waite, Tamasine Hedderly, Jean-Pierre Lin, Martin Smith, Alan Whone, Hardev Pall, Cathy White, Andrew Lux, Philip Jardine, Narinder Bajaj, Bryan Lynch, George Kirov, Sean O'Riordan, Michael Samuel, Timothy Lynch, Mary D. KingPatrick F. Chinnery, Thomas T. Warner, Derek J. Blake, Michael J. Owen, Huw R. Morris

^*Corresponding author for this work

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

92 Citations (Scopus)

Abstract

Myoclonus dystonia syndrome is a childhood onset hyperkinetic movement disorder characterized by predominant alcohol responsive upper body myoclonus and dystonia. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. Previous studies have suggested that patients with SGCE mutations may have an increased rate of psychiatric disorders. We established a cohort of patients with myoclonus dystonia syndrome and SGCE mutations to determine the extent to which psychiatric disorders form part of the disease phenotype. In all, 89 patients with clinically suspected myoclonus dystonia syndrome were recruited from the UK and Ireland. SGCE was analysed using direct sequencing and for copy number variants. In those patients where no mutation was found TOR1A (GAG deletion), GCH1, THAP1 and NKX2-1 were also sequenced. SGCE mutation positive cases were systematically assessed using standardized psychiatric interviews and questionnaires and compared with a disability-matched control group of patients with alcohol responsive tremor. Nineteen (21%) probands had a SGCE mutation, five of which were novel. Recruitment of family members increased the affected SGCE mutation positive group to 27 of whom 21 (77%) had psychiatric symptoms. Obsessive-compulsive disorder was eight times more likely (P <0.001) in mutation positive cases, compulsivity being the predominant feature (P <0.001). Generalized anxiety disorder (P = 0.003) and alcohol dependence (P = 0.02) were five times more likely in mutation positive cases than tremor controls. SGCE mutations are associated with a specific psychiatric phenotype consisting of compulsivity, anxiety and alcoholism in addition to the characteristic motor phenotype. SGCE mutations are likely to have a pleiotropic effect in causing both motor and specific psychiatric symptoms.

Original language	English
Pages (from-to)	294-303
Number of pages	10
Journal	Brain
Volume	136
Issue number	1
DOIs	https://doi.org/10.1093/brain/aws308
Publication status	Published - Jan 2013

Keywords

myoclonus dystonia
SGCE
psychiatric disorders
MYOCLONUS-DYSTONIA-SYNDROME
EPSILON-SARCOGLYCAN GENE
OBSESSIVE-COMPULSIVE DISORDER
INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW
DEEP BRAIN-STIMULATION
SPASMODIC TORTICOLLIS
ALCOHOL DEPENDENCE
FOCAL DYSTONIA
PHENOTYPIC SPECTRUM
RATING-SCALE

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/brain/aws308

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Peall, K. J., Smith, D. J., Kurian, M. A., Wardle, M., Waite, A. J., Hedderly, T., Lin, J.-P., Smith, M., Whone, A., Pall, H., White, C., Lux, A., Jardine, P., Bajaj, N., Lynch, B., Kirov, G., O'Riordan, S., Samuel, M., Lynch, T., ... Morris, H. R. (2013). SGCE mutations cause psychiatric disorders: clinical and genetic characterization. Brain, 136(1), 294-303. https://doi.org/10.1093/brain/aws308

@article{d459c1c22bc1413fb852d7894958ccfd,

title = "SGCE mutations cause psychiatric disorders: clinical and genetic characterization",

abstract = "Myoclonus dystonia syndrome is a childhood onset hyperkinetic movement disorder characterized by predominant alcohol responsive upper body myoclonus and dystonia. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. Previous studies have suggested that patients with SGCE mutations may have an increased rate of psychiatric disorders. We established a cohort of patients with myoclonus dystonia syndrome and SGCE mutations to determine the extent to which psychiatric disorders form part of the disease phenotype. In all, 89 patients with clinically suspected myoclonus dystonia syndrome were recruited from the UK and Ireland. SGCE was analysed using direct sequencing and for copy number variants. In those patients where no mutation was found TOR1A (GAG deletion), GCH1, THAP1 and NKX2-1 were also sequenced. SGCE mutation positive cases were systematically assessed using standardized psychiatric interviews and questionnaires and compared with a disability-matched control group of patients with alcohol responsive tremor. Nineteen (21%) probands had a SGCE mutation, five of which were novel. Recruitment of family members increased the affected SGCE mutation positive group to 27 of whom 21 (77%) had psychiatric symptoms. Obsessive-compulsive disorder was eight times more likely (P <0.001) in mutation positive cases, compulsivity being the predominant feature (P <0.001). Generalized anxiety disorder (P = 0.003) and alcohol dependence (P = 0.02) were five times more likely in mutation positive cases than tremor controls. SGCE mutations are associated with a specific psychiatric phenotype consisting of compulsivity, anxiety and alcoholism in addition to the characteristic motor phenotype. SGCE mutations are likely to have a pleiotropic effect in causing both motor and specific psychiatric symptoms.",

keywords = "myoclonus dystonia, SGCE, psychiatric disorders, MYOCLONUS-DYSTONIA-SYNDROME, EPSILON-SARCOGLYCAN GENE, OBSESSIVE-COMPULSIVE DISORDER, INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW, DEEP BRAIN-STIMULATION, SPASMODIC TORTICOLLIS, ALCOHOL DEPENDENCE, FOCAL DYSTONIA, PHENOTYPIC SPECTRUM, RATING-SCALE",

author = "Peall, {Kathryn J.} and Smith, {Daniel J.} and Kurian, {Manju A.} and Mark Wardle and Waite, {Adrian J.} and Tamasine Hedderly and Jean-Pierre Lin and Martin Smith and Alan Whone and Hardev Pall and Cathy White and Andrew Lux and Philip Jardine and Narinder Bajaj and Bryan Lynch and George Kirov and Sean O'Riordan and Michael Samuel and Timothy Lynch and King, {Mary D.} and Chinnery, {Patrick F.} and Warner, {Thomas T.} and Blake, {Derek J.} and Owen, {Michael J.} and Morris, {Huw R.}",

year = "2013",

month = jan,

doi = "10.1093/brain/aws308",

language = "English",

volume = "136",

pages = "294--303",

journal = "Brain",

issn = "0006-8950",

publisher = "Oxford University Press",

number = "1",

}

Peall, KJ, Smith, DJ, Kurian, MA, Wardle, M, Waite, AJ, Hedderly, T , Lin, J-P, Smith, M, Whone, A, Pall, H, White, C, Lux, A, Jardine, P, Bajaj, N, Lynch, B, Kirov, G, O'Riordan, S, Samuel, M, Lynch, T, King, MD, Chinnery, PF, Warner, TT, Blake, DJ, Owen, MJ & Morris, HR 2013, 'SGCE mutations cause psychiatric disorders: clinical and genetic characterization', Brain, vol. 136, no. 1, pp. 294-303. https://doi.org/10.1093/brain/aws308

TY - JOUR

T1 - SGCE mutations cause psychiatric disorders

T2 - clinical and genetic characterization

AU - Peall, Kathryn J.

AU - Smith, Daniel J.

AU - Kurian, Manju A.

AU - Wardle, Mark

AU - Waite, Adrian J.

AU - Hedderly, Tamasine

AU - Lin, Jean-Pierre

AU - Smith, Martin

AU - Whone, Alan

AU - Pall, Hardev

AU - White, Cathy

AU - Lux, Andrew

AU - Jardine, Philip

AU - Bajaj, Narinder

AU - Lynch, Bryan

AU - Kirov, George

AU - O'Riordan, Sean

AU - Samuel, Michael

AU - Lynch, Timothy

AU - King, Mary D.

AU - Chinnery, Patrick F.

AU - Warner, Thomas T.

AU - Blake, Derek J.

AU - Owen, Michael J.

AU - Morris, Huw R.

PY - 2013/1

Y1 - 2013/1

N2 - Myoclonus dystonia syndrome is a childhood onset hyperkinetic movement disorder characterized by predominant alcohol responsive upper body myoclonus and dystonia. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. Previous studies have suggested that patients with SGCE mutations may have an increased rate of psychiatric disorders. We established a cohort of patients with myoclonus dystonia syndrome and SGCE mutations to determine the extent to which psychiatric disorders form part of the disease phenotype. In all, 89 patients with clinically suspected myoclonus dystonia syndrome were recruited from the UK and Ireland. SGCE was analysed using direct sequencing and for copy number variants. In those patients where no mutation was found TOR1A (GAG deletion), GCH1, THAP1 and NKX2-1 were also sequenced. SGCE mutation positive cases were systematically assessed using standardized psychiatric interviews and questionnaires and compared with a disability-matched control group of patients with alcohol responsive tremor. Nineteen (21%) probands had a SGCE mutation, five of which were novel. Recruitment of family members increased the affected SGCE mutation positive group to 27 of whom 21 (77%) had psychiatric symptoms. Obsessive-compulsive disorder was eight times more likely (P <0.001) in mutation positive cases, compulsivity being the predominant feature (P <0.001). Generalized anxiety disorder (P = 0.003) and alcohol dependence (P = 0.02) were five times more likely in mutation positive cases than tremor controls. SGCE mutations are associated with a specific psychiatric phenotype consisting of compulsivity, anxiety and alcoholism in addition to the characteristic motor phenotype. SGCE mutations are likely to have a pleiotropic effect in causing both motor and specific psychiatric symptoms.

AB - Myoclonus dystonia syndrome is a childhood onset hyperkinetic movement disorder characterized by predominant alcohol responsive upper body myoclonus and dystonia. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. Previous studies have suggested that patients with SGCE mutations may have an increased rate of psychiatric disorders. We established a cohort of patients with myoclonus dystonia syndrome and SGCE mutations to determine the extent to which psychiatric disorders form part of the disease phenotype. In all, 89 patients with clinically suspected myoclonus dystonia syndrome were recruited from the UK and Ireland. SGCE was analysed using direct sequencing and for copy number variants. In those patients where no mutation was found TOR1A (GAG deletion), GCH1, THAP1 and NKX2-1 were also sequenced. SGCE mutation positive cases were systematically assessed using standardized psychiatric interviews and questionnaires and compared with a disability-matched control group of patients with alcohol responsive tremor. Nineteen (21%) probands had a SGCE mutation, five of which were novel. Recruitment of family members increased the affected SGCE mutation positive group to 27 of whom 21 (77%) had psychiatric symptoms. Obsessive-compulsive disorder was eight times more likely (P <0.001) in mutation positive cases, compulsivity being the predominant feature (P <0.001). Generalized anxiety disorder (P = 0.003) and alcohol dependence (P = 0.02) were five times more likely in mutation positive cases than tremor controls. SGCE mutations are associated with a specific psychiatric phenotype consisting of compulsivity, anxiety and alcoholism in addition to the characteristic motor phenotype. SGCE mutations are likely to have a pleiotropic effect in causing both motor and specific psychiatric symptoms.

KW - myoclonus dystonia

KW - SGCE

KW - psychiatric disorders

KW - MYOCLONUS-DYSTONIA-SYNDROME

KW - EPSILON-SARCOGLYCAN GENE

KW - OBSESSIVE-COMPULSIVE DISORDER

KW - INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW

KW - DEEP BRAIN-STIMULATION

KW - SPASMODIC TORTICOLLIS

KW - ALCOHOL DEPENDENCE

KW - FOCAL DYSTONIA

KW - PHENOTYPIC SPECTRUM

KW - RATING-SCALE

U2 - 10.1093/brain/aws308

DO - 10.1093/brain/aws308

M3 - Article

SN - 0006-8950

VL - 136

SP - 294

EP - 303

JO - Brain

JF - Brain

IS - 1

ER -

SGCE mutations cause psychiatric disorders: clinical and genetic characterization

Abstract

Keywords

UN SDGs

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