Hildebrandt F, Singh-Sawhney I, Schnieders B, Centofante L, Omran H, Pohlmann A, Schmaltz C, Wedekind H, Schubotz C, Antignac C
University Children's Hospital, Freiburg, Germany.
Am J Hum Genet. 1993 Dec;53(6):1256-61.
Familial juvenile nephronophthisis (NPH) is an autosomal recessive kidney disease that leads to end-stage renal failure in adolescence and is associated with the formation of cysts at the cortico-medullary junction of the kidneys. NPH is responsible for about 15% of end-stage renal disease in children, as shown by Kleinknecht and Habib. NPH in combination with autosomal recessive retinitis pigmentosa is known as the Senior-Løken syndrome (SLS) and exhibits renal pathology that is identical to NPH. We had excluded 40% of the human genome from linkage with a disease locus for NPH or SLS when Antignac et al. first demonstrated linkage for an NPH locus on chromosome 2. We present confirmation of linkage of an NPH locus to microsatellite markers on chromosome 2 in nine families with NPH. By linkage analysis with marker AFM262xb5 at locus D2S176, a maximum lod score of 5.05 at a theta max = .03 was obtained. In a large NPH family that yielded at D2S176 a maximum lod score of 2.66 at theta max = .0, markers AFM172xc3 and AFM016yc5, representing loci D2S135 and D2S110, respectively, were identified as flanking markers, thereby defining the interval for an NPH locus to a region of approximately 15 cM. Furthermore, the cytogenetic assignment of the NPH region was specified to 2p12-(2q13 or adjacent bands) by calculation of linkage between these flanking markers and markers with known unique cytogenetic assignment. The refined map may serve as a genetic framework for additional genetic and physical mapping of the region.
家族性青少年肾单位肾痨（NPH）是一种常染色体隐性遗传性肾脏疾病，可导致青少年期终末期肾衰竭，并与肾脏皮质-髓质交界处囊肿的形成有关。如克莱因克内希特和哈比所指出的，NPH约占儿童终末期肾病的15%。NPH与常染色体隐性遗传性视网膜色素变性合并存在时被称为Senior-Løken综合征（SLS），其肾脏病理表现与NPH相同。当安蒂尼亚克等人首次证明2号染色体上存在一个NPH基因座的连锁关系时，我们已将40%的人类基因组排除在与NPH或SLS疾病基因座的连锁关系之外。我们在9个NPH家族中证实了一个NPH基因座与2号染色体上微卫星标记的连锁关系。通过与位于D2S176基因座的标记AFM262xb5进行连锁分析，在θ最大值 = 0.03时获得了最大对数优势分数5.05。在一个大型NPH家族中，在D2S176基因座上，当θ最大值 = 0.0时最大对数优势分数为2.66，分别代表D2S135和D2S110基因座的标记AFM172xc3和AFM016yc5被确定为侧翼标记，从而将NPH基因座的区间定义为大约15厘摩的区域。此外，通过计算这些侧翼标记与具有已知独特细胞遗传学定位的标记之间的连锁关系，将NPH区域的细胞遗传学定位确定为2p12 -（2q13或相邻带）。这个精细的图谱可为该区域的进一步基因和物理图谱绘制提供遗传框架。
