Aminoff M, Tahvanainen E, Gräsbeck R, Weissenbach J, Broch H, de la Chapelle A
Department of Medical Genetics, University of Helsinki, Folkhälsan Institute of Genetics, Finland.
Am J Hum Genet. 1995 Oct;57(4):824-31.
Juvenile megaloblastic anemia caused by selective intestinal malabsorption of vitamin B12 has been considered a distinct condition displaying autosomal recessive inheritance. It appears to have a worldwide distribution, and comparatively high incidences were reported 30 years ago in Finland and Norway. More recently, the Mendelian inheritance of the condition has been questioned because almost no new cases have occurred in these populations. Here we report linkage studies assigning a recessive-gene locus for the disease to chromosome 10 in previously diagnosed multiplex families from Finland and Norway, proving the Mendelian mode of inheritance. The locus is tentatively assigned to the 6-cM interval between markers D10S548 and D10S466, with a multipoint maximum lod score (Zmax) of 5.36 near marker D10S1477. By haplotype analysis, the healthy sibs in these families did not appear to constitute any examples of nonpenetrance. We hypothesize that the paucity of new cases in these populations is due either to a dietary effect on the gene penetrance that has changed with time, or to a drop in the birth rate in subpopulations showing enrichment of the mutation, or to both of these causes.
由维生素B12选择性肠道吸收不良引起的青少年巨幼细胞贫血被认为是一种具有常染色体隐性遗传的独特病症。它似乎在全球范围内分布，30年前芬兰和挪威报告了相对较高的发病率。最近，由于这些人群中几乎没有新病例出现，这种病症的孟德尔遗传方式受到了质疑。在此，我们报告了连锁研究，在来自芬兰和挪威之前诊断的多个家庭中，将该疾病的一个隐性基因位点定位于10号染色体，证实了孟德尔遗传模式。该位点暂定位于标记D10S548和D10S466之间的6厘摩区间，在标记D10S1477附近多点最大对数优势分数（Zmax）为5.36。通过单倍型分析，这些家庭中的健康同胞似乎并不构成任何非外显的例子。我们推测，这些人群中新病例稀少的原因要么是饮食对随时间变化的基因外显率产生了影响，要么是显示突变富集的亚人群出生率下降，或者是这两个原因共同导致的。
