Genome-wide linkage scan maps ETINPH gene to chromosome 19q12-13.31

Jun Zhang, Christopher W. Carr, Daniele Rigamonti, Ahmed Badr

Research output: Contribution to journalArticle

Abstract

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)262-267
Number of pages6
JournalHuman Heredity
Volume69
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Normal Pressure Hydrocephalus
Essential Tremor
Chromosomes
Genome
Lod Score
Genes
Single Nucleotide Polymorphism
Inborn Genetic Diseases
Intracranial Hypertension
Tremor
Nervous System Diseases
Gait
Upper Extremity
Haplotypes
Dementia
Tremor, Hereditary Essential, And Idiopathic Normal Pressure Hydrocephalus
Population

Keywords

  • Essential tremor-idiopathic normal pressure hydrocephalus
  • ETINPH gene
  • Linkage analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Genome-wide linkage scan maps ETINPH gene to chromosome 19q12-13.31. / Zhang, Jun; Carr, Christopher W.; Rigamonti, Daniele; Badr, Ahmed.

In: Human Heredity, Vol. 69, No. 4, 04.2010, p. 262-267.

Research output: Contribution to journalArticle

Zhang, Jun ; Carr, Christopher W. ; Rigamonti, Daniele ; Badr, Ahmed. / Genome-wide linkage scan maps ETINPH gene to chromosome 19q12-13.31. In: Human Heredity. 2010 ; Vol. 69, No. 4. pp. 262-267.
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