Fatal infantile leukodystrophy - A severe variant of CACH/VWM syndrome, allelic to chromosome 3q27

被引:44
作者
Francalanci, P
Eymard-Pierre, E
Dionisi-Vici, C
Boldrini, R
Piemonte, F
Virgili, R
Fariello, G
Bosman, C
Santorelli, FM
Boespflug-Tanguy, O
Bertini, E
机构
[1] IRCCS, Bambino Gesu Res Hosp, Div Pathol, Rome, Italy
[2] IRCCS, Bambino Gesu Res Hosp, Dept Neurosci, Mol Med Unit, Rome, Italy
[3] Fac Med, INSERM, U384, Clermont Ferrand, France
关键词
D O I
10.1212/WNL.57.2.265
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To describe clinical and neuropathologic studies and linkage analysis on two sisters with a severe form of leukodystrophy. Methods: A detailed study was performed on the second sister. Genotyping markers for chromosome 3, including eight additional markers surrounding the vanishing white matter (VWM) locus, were used. Results: During the first year of life, two sisters developed a severe neurologic condition after an intercurrent infection. It was accompanied by irritability and stupor with rapid loss of their motor abilities. Results of extensive metabolic studies were negative. Brain MRI showed severe and diffuse abnormalities of the encephalic white matter. Neuropathologic examination showed a severe lack of myelin with diffuse vacuolating white matter lesions in the brain, associated with an increased density of oligodendrocytes and a reduced number of astrocytes on morphometric analysis. In sharp contrast, the spinal cord white matter was preserved. The affected sibpairs shared a common haplotype for a broad region in chromosome 3. They were homozygous between markers D3S1565 and D3S3669, including the VWM locus. Conclusions: This condition is an unusual variant of childhood ataxia with diffuse central hypomyelination (CACH)/VWM, with characteristic shrinking and perivascular clustering of astrocytes, Haplotype analysis suggests that this variant is allelic to the VWM locus located on chromosome 3q27.
引用
收藏
页码:265 / 270
页数:6
相关论文
共 17 条
[1]   Molecular water pumps and the aetiology of Canavan disease: A case of the sorcerer's apprentice [J].
Baslow, MH .
JOURNAL OF INHERITED METABOLIC DISEASE, 1999, 22 (02) :99-101
[2]   Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease [J].
Brenner, M ;
Johnson, AB ;
Boespflug-Tanguy, O ;
Rodriguez, D ;
Goldman, JE ;
Messing, A .
NATURE GENETICS, 2001, 27 (01) :117-120
[3]   SEQUENCE OF CENTRAL-NERVOUS-SYSTEM MYELINATION IN HUMAN INFANCY .1. AN AUTOPSY STUDY OF MYELINATION [J].
BRODY, BA ;
KINNEY, HC ;
KLOMAN, AS ;
GILLES, FH .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1987, 46 (03) :283-301
[4]   MYELIN OLIGODENDROCYTE GLYCOPROTEIN IS A UNIQUE MEMBER OF THE IMMUNOGLOBULIN SUPERFAMILY [J].
GARDINIER, MV ;
AMIGUET, P ;
LININGTON, C ;
MATTHIEU, JM .
JOURNAL OF NEUROSCIENCE RESEARCH, 1992, 33 (01) :177-187
[5]   DIFFUSE WHITE-MATTER DISEASE IN 3 CHILDREN - AN ENCEPHALOPATHY WITH UNIQUE FEATURES ON MAGNETIC-RESONANCE-IMAGING AND PROTON MAGNETIC-RESONANCE SPECTROSCOPY [J].
HANEFELD, F ;
HOLZBACH, U ;
KRUSE, B ;
WILICHOWSKI, E ;
CHRISTEN, HJ ;
FRAHM, J .
NEUROPEDIATRICS, 1993, 24 (05) :244-248
[6]   The gene for leukoencephalopathy with vanishing white matter is located on chromosome 3q27 [J].
Leegwater, PAJ ;
Könst, AAM ;
Kuyt, B ;
Sandkuijl, LA ;
Naidu, S ;
Oudejans, CBM ;
Schutgens, RBH ;
Pronk, JC ;
van der Knaap, MS .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (03) :728-734
[7]   GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination [J].
Liedtke, W ;
Edelmann, W ;
Bieri, PL ;
Chiu, FC ;
Cowan, NJ ;
Kucherlapati, R ;
Raine, CS .
NEURON, 1996, 17 (04) :607-615
[8]  
Messing A, 1998, AM J PATHOL, V152, P391
[9]  
Oh LYS, 1996, GLIA, V17, P237
[10]   Increased density of oligodendrocytes in childhood ataxia with diffuse central hypomyelination (CACH) syndrome:: neuropathological and biochemical study of two cases [J].
Rodriguez, D ;
Gelot, A ;
della Gaspera, B ;
Robain, O ;
Ponsot, G ;
Sarliève, LL ;
Ghandour, S ;
Pompidou, A ;
Dautigny, A ;
Aubourg, P ;
Pham-Dinh, D .
ACTA NEUROPATHOLOGICA, 1999, 97 (05) :469-480