HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hedera, P. Articles by Fink, J. K. Search for Related Content PubMed PubMed Citation Articles by Hedera, P. Articles by Fink, J. K. Related Collections Spastic paraplegia All Genetics

Spastic paraplegia, ataxia, mental retardation (SPAR)

A novel genetic disorder

From the Department of Neurology (Drs. Hedera, Rainier, Zhao, Trobe, and Wald, and Kluin), Department of Radiology (Dr. Eldevik), University of Michigan; and the Geriatric Research, Education, and Care Center (Dr. Fink), Ann Arbor Veteran’s Affairs Medical Center, MI; Department of Molecular Medicine (Drs. Schalling, Lindblad, and Yuan), Karolinska Institute, Stockholm, Sweden; and Department of Neurology (Dr. Ikeuchi), Brain Research Institute, Niigata, Japan.

Address correspondence and reprint requests to Dr. Fink, 5214 Cancer Center Geriatrics Center Building, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0940.

Objective: To describe a kindred with a dominantly inherited neurologic disorder manifested either as uncomplicated spastic paraplegia or ataxia, spastic paraplegia, and mental retardation.

Methods: Neurologic examinations and molecular genetic analysis (exclusion of known SCA and HSP genes and loci; and trinucleotide repeat expansion detection [RED]) were performed in six affected and four unaffected subjects in this family. MRI, electromyography (EMG), and nerve conduction studies were performed in three affected subjects.

Results: The phenotype of this dominantly inherited syndrome varied in succeeding generations. Pure spastic paraplegia was present in the earliest generation; subsequent generations had ataxia and mental retardation. MRI showed marked atrophy of the spinal cord in all patients and cerebellar atrophy in those with ataxia. Laboratory analysis showed that the disorder was not caused by mutations in genes that cause SCA-1, SCA-2, SCA-3, SCA-6, SCA-7, SCA-8, and SCA-12; not linked to other known loci for autosomal dominant ataxia (SCA-4, SCA-5, SCA-10, SCA-11, SCA-13, SCA-14, and SCA-16); and not linked to known loci for autosomal dominant hereditary spastic paraplegia (HSP) (SPG-3, SPG-4, SPG-6, SPG-8, SPG-9, SPG-10, SPG-12, and SPG-13) or autosomal recessive HSP SPG-7. Analysis of intergenerational differences in age at onset of symptoms suggests genetic anticipation. Using RED, the authors did not detect expanded CAG, CCT, TGG, or CGT repeats that segregate with the disease.

Conclusions: The authors describe an unusual, dominantly inherited neurologic disorder in which the phenotype (pure spastic paraplegia or spastic ataxia with variable mental retardation) differed in subsequent generations. The molecular explanation for apparent genetic anticipation does not appear to involve trinucleotide repeat expansion.

This article has been cited by other articles:

				G. S. Grieco, A. Malandrini, G. Comanducci, V. Leuzzi, M. Valoppi, A. Tessa, S. Palmeri, L. Benedetti, A. Pierallini, S. Gambelli, et al. Novel SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay type Neurology, January 13, 2004; 62(1): 103 - 106. [Abstract] [Full Text] [PDF]