Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: Hereditary inclusion body myopathy, paget disease of bone, and frontotemporal dementia

Margaret J. Kovach, Brook Waggoner, Suzanne M. Leal, David Gelber, Romesh Khardori, Mark A. Levenstien, Christy A. Shanks, Gregory Gregg, Muhammad T. Al-Lozi, Timothy Miller, Wojtek Rakowicz, Glenn Lopate, Juliane Florence, Guila Glosser, Zachary Simmons, John C. Morris, Michael P. Whyte, Alan Pestronk, Virginia E. Kimonis

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

Autosomal dominant myopathy, Paget disease of bone, and dementia constitute a unique disorder (MIM 605382). Here we describe the clinical, biochemical, radiological, and pathological characteristics of 49 affected (23 male, 26 female) individuals from four unrelated United States families. Among these affected individuals 90% have myopathy, 43% have Paget disease of bone, and 37% have premature frontotemporal dementia. EMG shows myopathic changes and muscle biopsy reveals nonspecific myopathic changes or blue-rimmed vacuoles. After candidate loci were excluded, a genome-wide screen in the large Illinois family showed linkage to chromosome 9 (maximum LOD score 3.64 with marker D9S301). Linkage analysis with a high density of chromosome 9 markers generated a maximum two-point LOD score of 9.29 for D9S1791, with a maximum multipoint LOD score of 12.24 between D9S304 and D9S1788. Subsequent evaluation of three additional families demonstrating similar clinical characteristics confirmed this locus, refined the critical region, and further delineated clinical features of this unique disorder. Hence, autosomal dominant inclusion body myopathy (HIBM), Paget disease of bone (PDB), and frontotemporal dementia (FTD) localizes to a 1.08-6.46 cM critical interval on 9p13.3-12 in the region of autosomal recessive IBM2.

Original languageEnglish (US)
Pages (from-to)458-475
Number of pages18
JournalMolecular Genetics and Metabolism
Volume74
Issue number4
DOIs
StatePublished - 2001

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Fingerprint Dive into the research topics of 'Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: Hereditary inclusion body myopathy, paget disease of bone, and frontotemporal dementia'. Together they form a unique fingerprint.

Cite this