Luo Y, Ceccherini I, Pasini B, Matera I, Bicocchi M P, Barone V, Bocciardi R, Kääriäinen H, Weber D, Devoto M
Laboratory of Molecular Genetics, G.Gaslini Institute, Genova, Quarto, Italy.
Hum Mol Genet. 1993 Nov;2(11):1803-8. doi: 10.1093/hmg/2.11.1803.
Tight linkage with the RET proto-oncogene (Zmax = 3.41 at theta = 0.00), analysis of recombinants and detection of a familial microdeletion in a large pedigree restrict the mapping of the Hirschsprung (HSCR) gene previously localized on proximal 10q. The molecular characterization of the familial microdeletion and of 3 additional cytogenetically visible de novo deletions, isolated in somatic cell hybrids, identify a smallest region of overlap of 250 Kb. This contains the RET proto-oncogene where missense mutations causing multiple endocrine neoplasia type 2A (MEN 2A) phenotype were recently found. The pentagastrin test (which detects preclinical forms of MEN 2A or B) is negative in adult HSCR patients with deletions of the RET gene. This represents a good candidate for the search of mutations causing HSCR.
与RET原癌基因紧密连锁（在θ = 0.00时，Zmax = 3.41），对重组体的分析以及在一个大家系中检测到家族性微缺失，限制了先前定位在10q近端的先天性巨结肠（HSCR）基因的定位。对家族性微缺失以及在体细胞杂种中分离出的另外3个细胞遗传学可见的新生缺失进行分子特征分析，确定了一个250 Kb的最小重叠区域。该区域包含RET原癌基因，最近在该基因中发现了导致2A型多发性内分泌肿瘤（MEN 2A）表型的错义突变。在患有RET基因缺失的成年HSCR患者中，五肽胃泌素试验（检测MEN 2A或B的临床前形式）呈阴性。这是寻找导致HSCR的突变的一个良好候选基因。
