Angrist M, Kauffman E, Slaugenhaupt S A, Matise T C, Puffenberger E G, Washington S S, Lipson A, Cass D T, Reyna T, Weeks D E
Department of Human Genetics, University of Pittsburgh, Pennsylvania 15261.
Nat Genet. 1993 Aug;4(4):351-6. doi: 10.1038/ng0893-351.
Hirschsprung disease (HSCR) is characterized by a congenital absence of enteric ganglia along a variable length of the intestine. Although long considered to be a multifactorial disease, we have identified linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby providing monogenic inheritance in some families. A maximum two-point lod score of 3.37 (theta = 0.045) was observed between HSCR and D10S176, under an incompletely penetrant dominant model. Multipoint, affecteds-only and non-parametric analyses supported this finding and localize this gene to a region of approximately 7 centiMorgans, in close proximity to the locus for multiple endocrine neoplasia type 2 (MEN2). The co-occurrence of these two entities in some families might be attributable to shared pathogenetic origins.
先天性巨结肠症（HSCR）的特征是沿肠道不同长度先天性缺乏肠神经节。尽管长期以来一直被认为是一种多因素疾病，但我们在五个HSCR家族的一个子集中发现了与10号染色体着丝粒周围区域的连锁关系，从而在一些家族中提供了单基因遗传的证据。在不完全显性遗传模型下，HSCR与D10S176之间观察到最大两点连锁值为3.37（θ = 0.045）。多点分析、仅对受累者的分析和非参数分析支持了这一发现，并将该基因定位到大约7厘摩的区域，该区域紧邻2型多发性内分泌肿瘤（MEN2）的基因座。在一些家族中这两种疾病的共同出现可能归因于共同的致病起源。
