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) Data Supplement All Versions of this Article: 01.wnl.0000294330.27058.61v1 70/21/1959    most recent 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 Orlacchio, A. Articles by Kawarai, T. Search for Related Content PubMed PubMed Citation Articles by Orlacchio, A. Articles by Kawarai, T. Related Collections Spastic paraplegia All Genetics Genetic linkage

Silver syndrome variant of hereditary spastic paraplegia

A locus to 4p and allelism with SPG4

From the Laboratorio di Neurogenetica (A.O., C.P., G.B.), CERC-IRCCS Santa Lucia, Rome; Dipartimento di Neuroscienze (A.O., C.R., V.M., G.B.) and Dipartimento di Diagnostica per Immagini e Radiologia Interventistica (F.G., R.F.), Università di Roma "Tor Vergata", Rome, Italy; and Department of Neurology (T.K.), Hyogo Brain and Heart Center, Himeji City, Japan.

Address correspondence and reprint requests to Dr. Antonio Orlacchio, Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, 64 Via del Fosso di Fiorano, Rome 00143, Italy a.orlacchio{at}hsantalucia.it

Objective: To perform a clinical and genetic study of two large Italian families (RM-36 and RM-51) showing the cardinal clinical features of Silver syndrome (SS), a rare dominantly inherited form of hereditary spastic paraplegia (HSP) complicated by amyotrophy of the small hand muscles.

Methods: Clinical assessment including neurophysiologic, neuropsychological, and neuroimaging evaluations. Genetic studies included linkage and sequence analyses.

Results: Using a genome-wide survey in the RM-36 family, a novel locus (SPG38) has been identified and mapped within the 13.1-cM region on chromosome 4p16-p15 between markers D4S432 and D4S1599. The RM-51 family was linked to the SPG4 locus at 2p21-p24 and sequence analysis of SPG4 showed a novel frameshift mutation p.Asp321GlyfsX6. Clinical examination of the affected members carrying the mutation showed high frequency of additional clinical features including decreased vibration sense, pes cavus, temporal lobe epilepsy, and cognitive impairment.

Conclusions: This study demonstrates evidence of a novel locus SPG38 for Silver syndrome (SS) and suggests that genetic defects in SPG4 might lead to broad clinical features overlapped with those of SS.

Abbreviations: AD = autosomal dominant; ALS = amyotrophic lateral sclerosis; AR = autosomal recessive; CAMCOG = Cambridge Cognitive Examination; CMAP = compound muscle action potential; CMCT = central motor conduction time; dHMN V = distal hereditary motor neuropathy type V; FDI = first dorsal interosseus; HS = hippocampal sclerosis; HSP = hereditary spastic paraplegia; LMN = lower motor neuron; MCI = mild cognitive impairment; MEP = motor evoked potential; MN = median nerve; mNCS = motor nerve conduction studies; MT = microtubule; PN = peroneal nerve; RFLP = restriction fragment length polymorphism; SCM = sternocleidomastoid muscle; sNCS = sensory nerve conduction studies; SS = Silver syndrome; SSEP = somatosensory evoked potential; TA = tibialis anterior; TLE = temporal lobe epilepsy; TN = tibial nerve; UMN = upper motor neuron; UN = ulnar nerve.

Supplemental data at www.neurology.org

Editorial, page 1948

e-Pub ahead of print on April 9, 2008, at www.neurology.org.

Supported by the Comitato Telethon Fondazione Onlus, the Amministrazione Autonoma dei Monopoli di Stato (AAMS), the city of Gubbio, Italy (grant n. GGP06209 to A.O.), the Italian Ministero della Salute (grants n. EBRI1.O, PS05.21, PS04.2O, and RF04.125O to A.O.), and the Lundbeck Foundation, Denmark (grant COFIN04.125O to A.O.).

Disclosure: The authors report no disclosures.

Received June 8, 2007. Accepted in final form September 18, 2007.

This article has been cited by other articles:

				L. P. Rowland and T. D. Bird Silver syndrome: The complexity of complicated hereditary spastic paraplegia Neurology, May 20, 2008; 70(21): 1948 - 1949. [Full Text] [PDF]