In:
Movement Disorders, Wiley, Vol. 35, No. 12 ( 2020-12), p. 2343-2347
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0885-3185
,
1531-8257
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2041249-6
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