Intrafamilial variability in hereditary spastic paraplegia associated with an SPG4 gene mutation

被引：40

作者：

Santorelli, FM

Patrono, C

Fortini, D

Tessa, A

Comanducci, G

Bertini, E

Pierallini, A

Amabile, GA

Casali, C

机构：

[1] IRCCS, Osped Bambino Gesu, I-00165 Rome, Italy

[2] Univ La Sapienza, Dept Neurol Sci & Neurosci, Rome, Italy

[3] Univ La Sapienza, Neurol Inst, Rome, Italy

来源：

NEUROLOGY | 2000年 / 55卷 / 05期

关键词：

D O I：

10.1212/WNL.55.5.702

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The authors studied a family with pure autosomal dominant spastic paraplegia (ADHSP) that showed a marked intrafamilial variability in both age at onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55. They found a novel mutation in the SPG4 gene, which segregates with the disease in six patients. The mutation affects the consensus donor splice site of SPG4 intron 16, resulting in a premature termination codon at amino acid 578. The data confirm the pathologic significance of SPG4 mutations in pure ADHSP and add to the list of known SPG4 allelic variants.

引用

收藏

页码：702 / 705

页数：4

相关论文

共 10 条

[1] STRUMPELLS FAMILIAL SPASTIC PARAPLEGIA - GENETICS AND NEUROPATHOLOGY [J].

BEHAN, WMH ;

MAIA, M .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1974, 37 (01) :8-20

[2] Phenotype of autosomal dominant spastic paraplegia linked to chromosome 2 [J].

Durr, A ;

Davoine, CS ;

Paternotte, C ;

vonFellenberg, J ;

Cogilnicean, S ;

Coutinho, P ;

Lamy, C ;

Bourgeois, S ;

Prudhomme, JF ;

Penet, C ;

Mas, JL ;

Burgunder, JM ;

Hazan, J ;

Weissenbach, J ;

Brice, A ;

Fontaine, B .

BRAIN, 1996, 119 :1487-1496

[3] Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia [J].

Fonknechten, N ;

Mavel, D ;

Byrne, P ;

Davoine, CS ;

Cruaud, C ;

Boentsch, D ;

Samson, D ;

Coutinho, P ;

Hutchinson, M ;

McMonagle, P ;

Burgunder, JM ;

Tartaglione, A ;

Heinzlef, O ;

Feki, I ;

Deufel, T ;

Parfrey, N ;

Brice, A ;

Fontaine, B ;

Prud'homme, JF ;

Weissenbach, J ;

Dürr, A ;

Hazan, J .

HUMAN MOLECULAR GENETICS, 2000, 9 (04) :637-644

[4] A new locus for autosomal dominant pure spastic paraplegia, on chromosome 2q24-q34 [J].

Fontaine, B ;

Davoine, CS ;

Dürr, A ;

Paternotte, C ;

Feki, I ;

Weissenbach, J ;

Hazan, J ;

Brice, A .

AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 66 (02) :702-707

[5] EXCLUSION OF THE CANDIDATE LOCUS FSP1 IN 6 FAMILIES WITH LATE-ONSET AUTOSOMAL-DOMINANT SPASTIC PARAPLEGIA [J].

FONTAINE, B ;

RIME, CS ;

HAZAN, J ;

DURR, A ;

STEVANIN, G ;

PENET, C ;

REBOUL, J ;

AGID, Y ;

LYONCAEN, O ;

BAUMANN, N ;

WEISSENBACH, J ;

BRICE, A .

NEUROMUSCULAR DISORDERS, 1995, 5 (01) :11-17

[6] HEREDITARY PURE SPASTIC PARAPLEGIA - A CLINICAL AND GENETIC-STUDY OF 22 FAMILIES [J].

HARDING, AE .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1981, 44 (10) :871-883

[7] Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia [J].

Hazan, J ;

Fonknechten, N ;

Mavel, D ;

Paternotte, C ;

Samson, D ;

Artiguenave, F ;

Davoine, CS ;

Cruaud, C ;

Dürr, A ;

Wincker, P ;

Brottier, P ;

Cattolico, L ;

Barbe, V ;

Burgunder, JM ;

Prud'homme, JF ;

Brice, A ;

Fontaine, B ;

Heilig, R ;

Weissenbach, J .

NATURE GENETICS, 1999, 23 (03) :296-303

[8] The AAA team: related ATPases with diverse functions [J].

Patel, S ;

Latterich, M .

TRENDS IN CELL BIOLOGY, 1998, 8 (02) :65-71

[9] Locus-phenotype correlations in autosomal dominant pure hereditary spastic paraplegia - A clinical and molecular genetic study of 28 United Kingdom families [J].

Reid, E ;

Grayson, C ;

Rogers, MT ;

Rubinsztein, DC .

BRAIN, 1999, 122 :1741-1755

[10]

Sherratt EJ, 1996, BIOTECHNIQUES, V20, P430