Basel-Vanagaite L, Straussberg R, Ovadia H, Kaplan A, Magal N, Shorer Z, Shalev H, Walsh C, Shohat M
Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, 49100, Israel.
Neurology. 2004 Jan 13;62(1):87-90. doi: 10.1212/01.wnl.0000101680.49036.69.
Infantile bilateral striatal necrosis (IBSN) encompasses several syndromes of bilateral symmetric degeneration of the caudate nucleus, putamen, and globus pallidus. Autosomal recessive IBSN is characterized clinically by developmental arrest beginning at age 7 to 15 months, dysphagia, choreoathetosis, pendular nystagmus and optic atrophy, and severe progressive atrophy of the basal ganglia on MRI.
To map the gene causing IBSN.
A 10-cM genome-wide linkage scan was initially performed on five affected and five unaffected individuals. The extended family was included in the analysis to narrow the candidate region. Logarithm of odds (LOD) score was calculated using the SUPERLINK program.
Linkage to the chromosomal region 19q13.32-13.41 was established (Z(max) = 6.27 at theta = 0.02 at locus D19S412). Recombination events and a common disease-bearing haplotype defined a critical region of 1.2 Mb between the loci D19S596 proximally and D19S867 distally.
IBSN maps to the chromosomal region 19q13.32-13.41. The presence of a common haplotype in all the patients suggests that the disease is caused by a single mutation derived from a single ancestral founder in all the families.
婴儿双侧纹状体坏死（IBSN）包括尾状核、壳核和苍白球双侧对称性变性的几种综合征。常染色体隐性IBSN的临床特征为7至15个月开始出现发育停滞、吞咽困难、舞蹈手足徐动症、摆动性眼球震颤和视神经萎缩，且MRI显示基底神经节严重进行性萎缩。
定位导致IBSN的基因。
最初对5名受累个体和5名未受累个体进行了全基因组10厘摩连锁扫描。将扩展家系纳入分析以缩小候选区域。使用SUPERLINK程序计算优势对数（LOD）得分。
确定与染色体区域19q13.32 - 13.41连锁（在基因座D19S412处，θ = 0.02时Z（max） = 6.27）。重组事件和一个常见的致病单倍型确定了一个关键区域，近端为基因座D19S596，远端为基因座D19S867，大小为1.2 Mb。
IBSN定位于染色体区域19q13.32 - 13.41。所有患者中存在常见单倍型表明该疾病是由所有家族中一个单一祖先奠基者的单一突变引起的。
