Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13

被引:115
作者
Taylor, TD
Litt, M
Kramer, P
Pandolfo, M
Angelini, L
Nardocci, N
Davis, S
Pineda, M
Hattori, H
Flett, PJ
Cilio, MR
Bertini, E
Hayflick, SJ
机构
[1] OREGON HLTH SCI UNIV, DEPT MOL & MED GENET, PORTLAND, OR 97201 USA
[2] OREGON HLTH SCI UNIV, DEPT NEUROL, PORTLAND, OR 97201 USA
[3] BAYLOR COLL MED, DEPT NEUROL, HOUSTON, TX 77030 USA
[4] IST NAZL NEUROL CARLO BESTA, DEPT CHILD NEUROL, I-20133 MILAN, ITALY
[5] AUCKLAND HOSP, NEUROSERV UNIT, AUCKLAND 1, NEW ZEALAND
[6] HOSP SAN JUAN DIOS, DEPT NEUROPEDIAT, BARCELONA 08034, SPAIN
[7] KYOTO UNIV, SCH MED, DEPT PEDIAT, KYOTO 606, JAPAN
[8] ADELAIDE CHILDRENS HOSP INC, DEPT PEDIAT, ADELAIDE, SA 5006, AUSTRALIA
[9] BAMBINO GESU PEDIAT HOSP, NEUROPHYSIOL UNIT, I-00165 ROME, ITALY
关键词
D O I
10.1038/ng1296-479
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Hallervorden-Spatz syndrome (HSS) (OMIM #234200) is a rare, autosomal recessive neurodegenerative disorder with brain iron accumulation as a prominent finding. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course(1). Histologic study reveals massive iron deposits in the basal ganglia. Systemic and cerebrospinal fluid iron levels are normal, as are plasma levels of ferritin, transferrin and ceruloplasmin. Conversely, in disorders of systemic iron overload, such as haemochromatosis, brain iron is not increased, which suggests that fundamental differences exist between brain and systemic iron metabolism and transport. In normal brain, non-haem iron accumulates regionally and is highest in basal ganglia(2). Pathologic brain iron accumulation is seen in common disorders, including Parkinson's disease(3,4), Alzheimer's disease(5,6) and Huntington disease(7). In order to gain insight into normal and abnormal brain iron transport, metabolism and function, our approach was to map the gene for HSS. A primary genome scan was performed using samples from a large, consanguineous family (HS1) (see Fig. 1). While this family was immensely powerful for mapping, the region demonstrating homozygosity in all affected members spans only 4 cM, requiring very close markers in order to detect linkage. The HSS gene maps to an interval flanked by D20S906 and D20S116 on chromosome 20p12.3-p13. Linkage was confirmed in nine additional families of diverse ethnic backgrounds.
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页码:479 / 481
页数:3
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