Matsumoto T, Kondoh T, Yoshimoto M, Fujieda K, Matsuura N, Matsuda I, Miike T, Yano K, Okuno A, Aoki Y
Department of Human Genetics, Nagasaki University School of Medicine, Japan.
Am J Med Genet. 1988 Nov;31(3):603-16. doi: 10.1002/ajmg.1320310315.
Five male Japanese patients with complex glycerol kinase deficiency (CGKD) and their relatives were studied clinically, cytogenetically, and molecular-genetically. All patients had muscular dystrophy or muscle weakness, mental retardation, congenital adrenal hypoplasia, and glycerol kinase deficiency. High-resolution GTG-banded chromosomes showed a microdeletion in the Xp21 region in all four patients examined and in all five mothers. Southern hybridizations, after digestions by restriction endonucleases, with various cloned DNAs (D2, 99-6, B24, C7, L1-4, cDMD13-14, J66-HI, P20, J-Bir, ERT87-30, ERT87-15, ERT87-8, ERT87-1, XJ-1.1, 754, cx5.7, and OTC-1) that are located around Xp21 also showed a deletion in the genome of all patients and mothers. Although the deletion differed in size among patients, a segment commonly absent was located between the genomic sequences corresponding to L1-4 and cDMD13-14. This finding indicated that the gene coding for glycerol kinase (GK) is located within this segment. A comparison of the clinical manifestations of the present five patients and reported CGKD or Duchenne muscular dystrophy (DMD) patients with DNA deletion suggests the existence of a certain gene responsible for gonadotropin deficiency (GTD). The result of the present study and results of previous studies suggest that genes for ornithine transcarbamylase (OTC), DMD, and GK and putative genes responsible for congenital adrenal hypoplasia (AHC) and GTD are arranged from telomere to centromere as pter--GTD--AHC--GK--DMD--OTC--cen.
对5名患有复杂甘油激酶缺乏症（CGKD）的日本男性患者及其亲属进行了临床、细胞遗传学和分子遗传学研究。所有患者均患有肌肉萎缩症或肌无力、智力发育迟缓、先天性肾上腺发育不全和甘油激酶缺乏症。高分辨率GTG带型染色体显示，在所有接受检查的4名患者以及所有5名母亲中，Xp21区域存在微缺失。用限制性内切酶消化后，与位于Xp21周围的各种克隆DNA（D2、99 - 6、B24、C7、L1 - 4、cDMD13 - 14、J66 - HI、P20、J - Bir、ERT87 - 30、ERT87 - 15、ERT87 - 8、ERT87 - 1、XJ - 1.1、754、cx5.7和OTC - 1）进行Southern杂交，结果也显示所有患者和母亲的基因组存在缺失。尽管患者之间缺失的大小不同，但在对应于L1 - 4和cDMD13 - 14的基因组序列之间存在一个共同缺失的片段。这一发现表明，编码甘油激酶（GK）的基因位于该片段内。将这5名患者与已报道的患有DNA缺失的CGKD或杜兴氏肌肉萎缩症（DMD）患者的临床表现进行比较，提示存在某个导致促性腺激素缺乏（GTD）的基因。本研究结果和先前的研究结果表明，鸟氨酸转氨甲酰酶（OTC）、DMD和GK的基因以及推测的负责先天性肾上腺发育不全（AHC）和GTD的基因，从端粒到着丝粒的排列顺序为pter--GTD--AHC--GK--DMD--OTC--cen。
