Schwartz M, Békássy A, Donnér M, Hertel T, Hreidarson S, Kerndrup G, Stormorken H, Stokland T, Tranebjaerg L, Orstavik K H, Skovby F
Department of Clinical Genetics, University Hospital, Rigshospitalet, Copenhagen, Denmark.
Thromb Haemost. 1996 Apr;75(4):546-50.
Twelve different mutations in the WASP gene were found in twelve unrelated families with Wiskott-Aldrich syndrome (WAS) or X-linked thrombocytopenia (XLT). Four frameshift, one splice, one nonsense mutation, and one 18-base-pair deletion were detected in seven patients with WAS. Only missense mutations were found in five patients diagnosed as having XLT. One of the nucleotide substitutions in exon 2 (codon 86) results in an Arg to Cys replacement. Two other nucleotide substitutions in this codon, R86L and R86H, have been reported previously, both giving rise to typical WAS symptoms, indicating a mutational hot spot in this codon. The finding of mutations in the WASP gene in both WAS and XLT gives further evidence of these syndromes being allelic. The relatively small size of the WASP gene facilitates the detection of mutations and a reliable diagnosis of both carriers and affected fetuses in families with WAS or XLT.
在12个患有威斯科特-奥尔德里奇综合征（WAS）或X连锁血小板减少症（XLT）的无关家族中，发现了WASP基因的12种不同突变。在7例WAS患者中检测到4种移码突变、1种剪接突变、1种无义突变和1种18个碱基对的缺失。在5例被诊断为XLT的患者中仅发现错义突变。外显子2（密码子86）中的一个核苷酸替换导致精氨酸被半胱氨酸取代。此前已报道该密码子中的另外两个核苷酸替换，即R86L和R86H，均导致典型的WAS症状，表明该密码子存在突变热点。在WAS和XLT中均发现WASP基因突变，进一步证明了这些综合征是等位基因。WASP基因相对较小，便于检测突变，并对WAS或XLT家族中的携带者和受影响胎儿进行可靠诊断。
