Genome-wide linkage scan maps ETINPH gene to chromosome 19q12-13.31.
OBJECTIVE
Essential tremor (ET), one of the most common neurological disorders, comprises uncontrollable tremor, usually in the upper extremities. Idiopathic normal pressure hydrocephalus (iNPH) features ventricular enlargement in the absence of elevated intracranial pressure; its three cardinal symptoms are gait impairment, incontinence, and dementia. iNPH is among the most common medical problems in the older population. To date, the genetic etiologies of ET and iNPH remain largely elusive.


METHODS
We previously identified a large kindred in which the affected members developed ET in adolescence or young adulthood and iNPH when elderly, in that case called ETINPH. Employing two different genotyping microarrays and two- or multipoint linkage analysis strategies, genome-wide linkage scans were performed.


RESULTS
We mapped the ETINPH locus to chromosome 19q12-13.31. Fine-mapping in this region revealed a maximum two-point lod score of 2.8 at rs2023865 and a maximum multipoint lod score of 17.9 at rs9304878. By haplotype construction, a (conservatively) approximately 17-cM critical region from SNP rs11084582 to SNP rs7258420 was defined. This region contains several neuronal genes that constitute tantalizing etiological candidates for ETINPH.


CONCLUSIONS
The importance of uncovering the genetic etiology of this disorder is irrefutable, as such a discovery could offer valuable insights into ET, iNPH, and related neurological conditions.
Zhang
Jun
J
Departments of Anesthesiology and Neurosurgery, Center for Neurosciences, Texas Tech University Health Science Center, El Paso, TX, USA. jun.zhang2000@gmail.com
Carr
Christopher W
CW
Rigamonti
Daniele
D
Badr
Ahmed
A
D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000235:genetics*; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide