Kaye E M, Shalish C, Livermore J, Taylor H A, Stevenson R E, Breakefield X O
Molecular Neurogenetics Unit, Massachusetts General Hospital East, Boston, USA.
J Child Neurol. 1997 Jun;12(4):242-7. doi: 10.1177/088307389701200404.
Three unrelated North American cases with slowly progressive forms of GM1 gangliosidosis were found to have two unique point mutations and a 9 bp insertion in the coding region of the gene encoding beta-galactosidase. Case 1 was noted to have a 9 bp insertion ¿CAGAATTTT¿ on one allele between nucleotides 730 and 731 with no other mutations identified in the other allele. In case 2, two point mutations were found: a unique G-->A transition at nucleotide 602 causing an Arg-->His substitution in codon 201 (mutation R201H); and a previously identified G-->T transition at nucleotide 1527 causing a Trp-->Cys substitution in codon 509 (mutation W509C), which has been noted in adult and chronic forms of GM1 gangliosidosis. Case 3 had a unique point mutation (A-->G transition at nucleotide 797) resulting in a Asn-->Ser amino acid substitution in codon 266 (mutation N266S), with no other mutations found in the same or the other allele. Single-strand conformation polymorphism performed on over 100 controls did not demonstrate the presence of the point mutations R201H or N266S. Also, the mutant proteins coded by the two point mutations did not show enzymatic activity in the Cos-1 cell expression system confirming that these mutations are associated with low enzyme activity.
在北美发现了三例与其他病例无关的、患有缓慢进展型GM1神经节苷脂贮积症的病例，其编码β-半乳糖苷酶的基因编码区存在两个独特的点突变和一个9碱基对的插入。病例1在一个等位基因的730和731核苷酸之间有一个9碱基对的插入“CAGAATTTT”，另一个等位基因未发现其他突变。病例2发现了两个点突变：核苷酸602处独特的G→A转换，导致密码子201中的精氨酸被组氨酸取代（R201H突变）；以及先前在核苷酸1527处发现的G→T转换，导致密码子509中的色氨酸被半胱氨酸取代（W509C突变），该突变在成人和慢性GM1神经节苷脂贮积症中已有报道。病例3有一个独特的点突变（核苷酸797处A→G转换），导致密码子266中的天冬酰胺被丝氨酸取代（N266S突变），同一等位基因或另一个等位基因均未发现其他突变。对100多个对照进行的单链构象多态性分析未显示R201H或N266S点突变的存在。此外，由这两个点突变编码的突变蛋白在Cos-1细胞表达系统中未显示酶活性，证实这些突变与低酶活性相关。
