Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene
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Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene. / 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.
In: Movement Disorders, Vol. 35, No. 12, 2020, p. 2343-2347.Research output: Contribution to journal › Journal article › Research › peer-review
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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.
PY - 2020
Y1 - 2020
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.
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.
KW - dyskinesia
KW - dystonia
KW - nail-patella syndrome
KW - paroxysmal dyskinesia
U2 - 10.1002/mds.28244
DO - 10.1002/mds.28244
M3 - Journal article
C2 - 32949189
AN - SCOPUS:85091018857
VL - 35
SP - 2343
EP - 2347
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
IS - 12
ER -
ID: 249107641