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Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene

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@article{85ee237906ad4f85abfa1f7080196634,
title = "Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene",
abstract = "BACKGROUND: In a Danish family, multiple individuals in five generations present with early-onset paroxysmal cranial dyskinesia, musculoskeletal abnormalities, and kidney dysfunction.OBJECTIVE: To demonstrate linkage and to identify the underlying genetic cause of disease.METHODS: Genome-wide single-nucleotide polymorphisms analysis, Sequence-Tagged-Site marker analyses, exome sequencing, and Sanger sequencing were performed.RESULTS: Linkage analyses identified a candidate locus on chromosome 9. Exome sequencing revealed a novel variant in LMX1B present in all affected individuals, logarithm of the odds (LOD) score of z = 6.54, predicted to be damaging. Nail-patella syndrome (NPS) is caused by pathogenic variants in LMX1B encoding a transcription factor essential to cytoskeletal and kidney growth and dopaminergic and serotonergic network development. NPS is characterized by abnormal musculoskeletal features and kidney dysfunction. Movement disorders have not previously been associated with NPS.CONCLUSIONS: Paroxysmal dyskinesia is a heretofore unrecognized feature of the NPS spectrum. The pathogenic mechanism might relate to aberrant dopaminergic circuits. {\textcopyright} 2020 International Parkinson and Movement Disorder Society.",
keywords = "dyskinesia, dystonia, nail-patella syndrome, paroxysmal dyskinesia",
author = "Sara Bech and Annemette L{\o}kkegaard and Nielsen, {Troels T} and Anne N{\o}rrem{\o}lle and Sabine Gr{\o}nborg and Lis Hasholt and Steffensen, {Gudrun K} and Gabor Graehn and Olesen, {Jess H} and Niels Tommerup and Yuan Mang and Mads Bak and Nielsen, {J{\o}rgen E} and Hans Eiberg and Hjermind, {Lena E}",
note = "{\textcopyright} 2020 International Parkinson and Movement Disorder Society.",
year = "2020",
month = dec,
doi = "10.1002/mds.28244",
language = "English",
volume = "35",
pages = "2343--2347",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "John/Wiley & Sons, Inc. John/Wiley & Sons Ltd",
number = "12",

}

RIS

TY - JOUR

T1 - Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene

AU - Bech, Sara

AU - Løkkegaard, Annemette

AU - Nielsen, Troels T

AU - Nørremølle, Anne

AU - Grønborg, Sabine

AU - Hasholt, Lis

AU - Steffensen, Gudrun K

AU - Graehn, Gabor

AU - Olesen, Jess H

AU - Tommerup, Niels

AU - Mang, Yuan

AU - Bak, Mads

AU - Nielsen, Jørgen E

AU - Eiberg, Hans

AU - Hjermind, Lena E

N1 - © 2020 International Parkinson and Movement Disorder Society.

PY - 2020/12

Y1 - 2020/12

N2 - BACKGROUND: In a Danish family, multiple individuals in five generations present with early-onset paroxysmal cranial dyskinesia, musculoskeletal abnormalities, and kidney dysfunction.OBJECTIVE: To demonstrate linkage and to identify the underlying genetic cause of disease.METHODS: Genome-wide single-nucleotide polymorphisms analysis, Sequence-Tagged-Site marker analyses, exome sequencing, and Sanger sequencing were performed.RESULTS: Linkage analyses identified a candidate locus on chromosome 9. Exome sequencing revealed a novel variant in LMX1B present in all affected individuals, logarithm of the odds (LOD) score of z = 6.54, predicted to be damaging. Nail-patella syndrome (NPS) is caused by pathogenic variants in LMX1B encoding a transcription factor essential to cytoskeletal and kidney growth and dopaminergic and serotonergic network development. NPS is characterized by abnormal musculoskeletal features and kidney dysfunction. Movement disorders have not previously been associated with NPS.CONCLUSIONS: Paroxysmal dyskinesia is a heretofore unrecognized feature of the NPS spectrum. The pathogenic mechanism might relate to aberrant dopaminergic circuits. © 2020 International Parkinson and Movement Disorder Society.

AB - BACKGROUND: In a Danish family, multiple individuals in five generations present with early-onset paroxysmal cranial dyskinesia, musculoskeletal abnormalities, and kidney dysfunction.OBJECTIVE: To demonstrate linkage and to identify the underlying genetic cause of disease.METHODS: Genome-wide single-nucleotide polymorphisms analysis, Sequence-Tagged-Site marker analyses, exome sequencing, and Sanger sequencing were performed.RESULTS: Linkage analyses identified a candidate locus on chromosome 9. Exome sequencing revealed a novel variant in LMX1B present in all affected individuals, logarithm of the odds (LOD) score of z = 6.54, predicted to be damaging. Nail-patella syndrome (NPS) is caused by pathogenic variants in LMX1B encoding a transcription factor essential to cytoskeletal and kidney growth and dopaminergic and serotonergic network development. NPS is characterized by abnormal musculoskeletal features and kidney dysfunction. Movement disorders have not previously been associated with NPS.CONCLUSIONS: Paroxysmal dyskinesia is a heretofore unrecognized feature of the NPS spectrum. The pathogenic mechanism might relate to aberrant dopaminergic circuits. © 2020 International Parkinson and Movement Disorder Society.

KW - dyskinesia

KW - dystonia

KW - nail-patella syndrome

KW - paroxysmal dyskinesia

UR - http://www.scopus.com/inward/record.url?scp=85091018857&partnerID=8YFLogxK

U2 - 10.1002/mds.28244

DO - 10.1002/mds.28244

M3 - Journal article

C2 - 32949189

VL - 35

SP - 2343

EP - 2347

JO - Movement Disorders

JF - Movement Disorders

SN - 0885-3185

IS - 12

ER -

ID: 61264669