Russell L J, DiGiovanna J J, Hashem N, Compton J G, Bale S J
Genetic Studies Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-2757.
Am J Hum Genet. 1994 Dec;55(6):1146-52.
We have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of the enzymes responsible for cross-linking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI (Z = 9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates.
我们已经对板层状鱼鳞病（LI）的基因座进行了定位，板层状鱼鳞病是一种常染色体隐性皮肤病，其特征为表皮角质化异常。对表现出严重LI症状的近交和远交家系进行分析发现，与14号染色体q11区域内9.3厘摩范围内的几个标记完全连锁。在近交家系中，患病个体在该区域的标记上也表现出显著的纯合性。基于连锁分析的遗传咨询和产前诊断现已可供信息充分的高危家系使用。几个转录基因已被定位到包含LI基因的14号染色体区域。转谷氨酰胺酶1基因（TGM1）编码一种在角质层形成过程中负责表皮蛋白交联的酶，该基因定位于此区间。TGM1基因座与LI完全连锁（Z = 9.11），这表明TGM1是进一步研究该疾病的良好候选基因。四种丝氨酸蛋白酶的基因也定位于此区域，但仅在造血细胞或肥大细胞中表达，因此它们作为候选基因的可能性较小。
