Adams E M, Becker J A, Griffith L, Segal A, Plotz P H, Raben N
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hum Mutat. 1997;10(2):128-34. doi: 10.1002/(SICI)1098-1004(1997)10:2<128::AID-HUMU5>3.0.CO;2-G.
The recessively inherited deficiency of acid alpha-glucosidase (GAA) called Glycogenosis Type II is expressed as three different phenotypes: infantile, juvenile, and adult. At the molecular level, infantile and adult forms of the disease have been extensively studied, but little is known regarding the genetic defects associated with the juvenile form. We describe a novel mutation that defines the intermediate juvenile phenotype in a compound heterozygous patient. A transversion of t to g in intron 6 at position -22 creates a cryptic acceptor site and results in unusual splicing abnormality: insertion of 21 nucleotides of the intronic sequence into mRNA and removal of exon 6 without disruption of the reading frame. The second mutation, Arg854Stop in exon 18, had been previously identified in another African-American patient (Hermans et al., 1993a). Family study indicates that a silent allele harboring the Arg854Stop mutation in our patient is inherited from the patient's father, who is also African-American, thus suggesting a common mutation in this population.
隐性遗传的酸性α-葡萄糖苷酶（GAA）缺乏症称为糖原贮积病II型，表现为三种不同的表型：婴儿型、青少年型和成人型。在分子水平上，已对该疾病的婴儿型和成人型进行了广泛研究，但对于与青少年型相关的基因缺陷了解甚少。我们描述了一种新的突变，该突变在一名复合杂合子患者中定义了中间型青少年表型。内含子6中-22位的t到g颠换产生了一个隐蔽的剪接受体位点，并导致异常的剪接异常：内含子序列的21个核苷酸插入mRNA，外显子6被去除，而阅读框未被破坏。第二个突变是外显子18中的Arg854Stop，此前已在另一名非裔美国患者中鉴定出（Hermans等人，1993a）。家系研究表明，我们患者中携带Arg854Stop突变的沉默等位基因是从患者的父亲那里遗传而来的，他也是非裔美国人，因此表明该人群中存在常见突变。
