TY - JOUR
T1 - The gene for leukoencephalopathy with vanishing white matter is located on chromosome 3q27
AU - Leegwater, Peter A.J.
AU - Könst, Andrea A.M.
AU - Kuyt, Bertus
AU - Sandkuijl, Lodewijk A.
AU - Naidu, Sakku Bai
AU - Oudejans, Cees B.M.
AU - Schutgens, Ruud B.H.
AU - Pronk, Jan C.
AU - Van Der Knaap, Marjo S.
N1 - Funding Information:
We thank G. Pals, Ph.D., of the Department for Human Genetics, Free University, Amsterdam, The Netherlands, for providing the genomewide marker set. For referral of families with VWM, we acknowledge Drs. H. Stroink, Rotterdam; F. J. M. Gabreëls and J. J. Rotteveel, Nijmegen, The Netherlands; P. G. Barth, Amsterdam; J. F. de Rijk van Andel, Breda, The Netherlands; R. Surtees, E. Llewellyn, and C. de Sousa, London; J. T. R. Clarke, A. Feigenbaum, and S. Blaser, Toronto; E. Franzoni, Bologna; E. Gut, Allensbach, Germany; and M. S. Scher, Cleveland. Dr. J. M. Powers, Rochester, NY, is acknowledged for sending brain tissue. Tissue specimens obtained from the National Neurological Research Specimen Bank, Veterans Administration Medical Center, Wadsworth Division, Los Angeles, which is sponsored by the National Institute of Neurological Disorders and Stroke/National Institute of Mental Health, the National Multiple Sclerosis Society, the Hereditary Disease Foundation, and the Veterans Health Services and Research Administration, Department of Veterans Affairs.
PY - 1999
Y1 - 1999
N2 - Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder with normal early development and, usually, childhood- onset neurological deterioration. At present, diagnosis of VWM is based on clinical examination and the results of repeat magnetic resonance imaging and magnetic resonance spectroscopy, which show that, with time, increasing amounts of the cerebral white matter vanish and are replaced by cerebrospinal fluid. We have performed a genome linkage screening of a panel of 19 families of different ethnic origins. Significant linkage to chromosome 3q27 was observed in a 7-cM interval between markers D3S3730 and D3S3592, with a maximum multipoint LOD score of 5.1 calculated from the entire data set. The results of genealogical studies have suggested that seven parents in four Dutch families with VWM may have inherited an allele for the disease from a common ancestor who lived at least eight generations ago. Analysis of these families provided further evidence for the localization of the gene for VWM to 3q27. The patients shared a haplotype spanning 5 cM between markers D3S1618 and D3S3592. In one family of a different ethnic background, the patient had, in the same region, homozygosity for 13 consecutive markers spanning at least 12 cM, suggesting consanguinity between the parents. A healthy sibling of this patient had the same homozygous haplotype, which suggests that the healthy sibling is presymptomatic for the disease.
AB - Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder with normal early development and, usually, childhood- onset neurological deterioration. At present, diagnosis of VWM is based on clinical examination and the results of repeat magnetic resonance imaging and magnetic resonance spectroscopy, which show that, with time, increasing amounts of the cerebral white matter vanish and are replaced by cerebrospinal fluid. We have performed a genome linkage screening of a panel of 19 families of different ethnic origins. Significant linkage to chromosome 3q27 was observed in a 7-cM interval between markers D3S3730 and D3S3592, with a maximum multipoint LOD score of 5.1 calculated from the entire data set. The results of genealogical studies have suggested that seven parents in four Dutch families with VWM may have inherited an allele for the disease from a common ancestor who lived at least eight generations ago. Analysis of these families provided further evidence for the localization of the gene for VWM to 3q27. The patients shared a haplotype spanning 5 cM between markers D3S1618 and D3S3592. In one family of a different ethnic background, the patient had, in the same region, homozygosity for 13 consecutive markers spanning at least 12 cM, suggesting consanguinity between the parents. A healthy sibling of this patient had the same homozygous haplotype, which suggests that the healthy sibling is presymptomatic for the disease.
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U2 - 10.1086/302548
DO - 10.1086/302548
M3 - Article
C2 - 10441579
AN - SCOPUS:0033361759
SN - 0002-9297
VL - 65
SP - 728
EP - 734
JO - American journal of human genetics
JF - American journal of human genetics
IS - 3
ER -