GFAP mutations, age at onset, and clinical subtypes in Alexander disease

被引：189

作者：

Prust, M. ^{[1
]}

Wang, J. ^{[1
]}

Morizono, H.

Messing, A. ^{[2
]}

Brenner, M. ^{[3
]}

Gordon, E. ^{[4
]}

Hartka, T. ^{[1
]}

Sokohl, A. ^{[1
]}

Schiffmann, R. ^{[5
]}

Gordish-Dressman, H. ^{[1
]}

Albin, R. ^{[6
]}

Amartino, H. ^{[7
]}

Brockman, K. ^{[8
]}

Dinopoulos, A. ^{[9
]}

Dotti, M. T. ^{[10
]}

Fain, D. ^{[11
]}

Fernandez, R. ^{[12
]}

Ferreira, J.

Fleming, J.

Gill, D. ^{[13
]}

Griebel, M. ^{[14
]}

Heilstedt, H. ^{[5
]}

Kaplan, P. ^{[15
]}

Lewis, D. ^{[16
]}

Nakagawa, M. ^{[17
]}

Pedersen, R. ^{[18
]}

Reddy, A. ^{[19
]}

Sawaishi, Y. ^{[20
]}

Schneider, M. ^{[21
]}

Sherr, E. ^{[22
]}

Takiyama, Y. ^{[23
]}

Wakabayashi, K. ^{[24
]}

Gorospe, J. R. ^{[25
]}

Vanderver, A. ^{[1
]}

机构：

[1] Childrens Natl Med Ctr, Washington, DC 20010 USA

[2] Univ Wisconsin, Madison, WI 53706 USA

[3] Univ Alabama, Birmingham, AL USA

[4] Coriell Inst Med Res, Camden, NJ USA

[5] Baylor Res Inst, Waco, TX USA

[6] Univ Michigan, Vet Affairs Ann Arbor Hlth Syst Geriatr Res Educ, Ann Arbor, MI 48109 USA

[7] Hosp Univ Austral, Pilar, Argentina

[8] Univ Gottingen, Gottingen, Germany

[9] Univ Athens, Athens, Greece

[10] Univ Siena, I-53100 Siena, Italy

[11] Bronson Hosp, Kalamazoo, MI USA

[12] Univ S Florida, Sch Med, Tampa, FL 33620 USA

[13] Childrens Hosp Westmead, Dept Neurol, Sydney, NSW, Australia

[14] Univ Arkansas Med Sci, Little Rock, AR 72205 USA

[15] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[16] Univ Med Ctr, Durham, NC USA

[17] Kyoto Prefectural Univ Med, Kyoto, Japan

[18] Tripler Army Med Ctr, Honolulu, HI 96859 USA

[19] Childrens Hosp Alabama, Birmingham, AL USA

[20] Akita Prefectural Ctr Dev & Disabil, Akita, Japan

[21] So Illinois Univ, Sch Med, Springfield, IL USA

[22] Univ Calif San Francisco, San Francisco, CA 94143 USA

[23] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Yamanashi, Japan

[24] Showa Univ, Fujigaoka Hosp, Yokohama, Kanagawa 227, Japan

[25] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA

来源：

NEUROLOGY | 2011年 / 77卷 / 13期

关键词：

FIBRILLARY ACIDIC PROTEIN; JUVENILE FORM; GENE; PATIENT; SPECTROSCOPY; DIAGNOSIS; ATAXIA;

D O I：

10.1212/WNL.0b013e3182309f72

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: To characterize Alexander disease (AxD) phenotypes and determine correlations with age at onset (AAO) and genetic mutation. AxD is an astrogliopathy usually characterized on MRI by leukodystrophy and caused by glial fibrillary acidic protein (GFAP) mutations. Methods: We present 30 new cases of AxD and reviewed 185 previously reported cases. We conducted Wilcoxon rank sum tests to identify variables scaling with AAO, survival analysis to identify predictors of mortality, and chi(2) tests to assess the effects of common GFAP mutations. Finally, we performed latent class analysis (LCA) to statistically define AxD subtypes. Results: LCA identified 2 classes of AxD. Type I is characterized by early onset, seizures, macrocephaly, motor delay, encephalopathy, failure to thrive, paroxysmal deterioration, and typical MRI features. Type II is characterized by later onset, autonomic dysfunction, ocular movement abnormalities, bulbar symptoms, and atypical MRI features. Survival analysis predicted a nearly 2-fold increase in mortality among patients with type I AxD relative to those with type II. R79 and R239 GFAP mutations were most common (16.6% and 20.3% of all cases, respectively). These common mutations predicted distinct clinical outcomes, with R239 predicting the most aggressive course. Conclusions: AAO and the GFAP mutation site are important clinical predictors in AxD, with clear correlations to defined patterns of phenotypic expression. We propose revised AxD subtypes, type I and type II, based on analysis of statistically defined patient groups. Neurology (R) 2011; 77: 1287-1294

引用

页码：1287 / 1294

页数：8

共 40 条

[1] PROGRESSIVE FIBRINOID DEGENERATION OF FIBRILLARY ASTROCYTES ASSOCIATED WITH MENTAL RETARDATION IN A HYDROCEPHALIC INFANT [J].