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Paroxysmal Cranial Dyskinesia and Nail‐Patella Syndrome Caused by a Novel Variant in the LMX1B Gene
Author(s) -
Bech Sara,
Løkkegaard Annemette,
Nielsen Troels T.,
Nørremølle Anne,
Grønborg Sabine,
Hasholt Lis,
Steffensen Gudrun K.,
Graehn Gabor,
Olesen Jess H.,
Tommerup Niels,
Mang Yuan,
Bak Mads,
Nielsen Jørgen E.,
Eiberg Hans,
Hjermind Lena E.
Publication year - 2020
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28244
Subject(s) - genetics , exome sequencing , dyskinesia , exome , sanger sequencing , biology , candidate gene , genetic linkage , locus (genetics) , bioinformatics , medicine , gene , disease , parkinson's disease , mutation , pathology
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. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.