Kroos M A, Van der Kraan M, Van Diggelen O P, Kleijer W J, Reuser A J
Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
Hum Mutat. 1997;9(1):17-22. doi: 10.1002/(SICI)1098-1004(1997)9:1<17::AID-HUMU3>3.0.CO;2-M.
Mutation analysis was performed in a nonconsanguineous Dutch caucasian family with a grandfather presenting the first symptoms of glycogen storage disease type II (acid alpha-glucosidase deficiency) in the sixth decade of life and a grandchild with onset of symptoms shortly after birth. The grandfather was identified as compound heterozygote having the IVS1(-13T-->G)/delta T525 combination of mutant acid alpha-glucosidase alleles, the affected third generation offspring as homozygote delta T525/delta T525. The disease phenotypes in this family are in accordance with the genotypes since the IVS1(-13T-->G) mutation reduces acid alpha-glucosidase synthesis by 60 to 80%, whereas the delta T525 mutation completely prohibits the formation of catalytically active enzyme. Four additional families were identified with patients homozygote for delta T525 and five others with an equally deleterious delta T525/delta exon 18 genotype. The nine latter patients had typically the infantile form of glycogen storage disease type II. The genotype-phenotype correlation is irrefutable.
对一个非近亲婚配的荷兰白种人家族进行了突变分析。该家族中，一位祖父在60岁左右首次出现糖原贮积病II型（酸性α-葡萄糖苷酶缺乏症）的症状，一名孙辈在出生后不久就出现了症状。祖父被鉴定为复合杂合子，具有IVS1(-13T→G)/δT525突变酸性α-葡萄糖苷酶等位基因组合，受影响的第三代后代为纯合子δT525/δT525。该家族中的疾病表型与基因型相符，因为IVS1(-13T→G)突变使酸性α-葡萄糖苷酶的合成减少60%至80%，而δT525突变则完全阻止了催化活性酶的形成。另外还鉴定出4个家族，其患者为δT525纯合子，另有5个家族具有同样有害的δT525/δ外显子18基因型。后9名患者通常患有婴儿型糖原贮积病II型。基因型与表型的相关性是无可辩驳的。
