Castellani C, Bonizzato A, Mastella G
Cystic Fibrosis Centre, Ospedale Civile Maggiore, Verona, Italy.
J Med Genet. 1997 Apr;34(4):297-301. doi: 10.1136/jmg.34.4.297.
Neonates positive for immunoreactive trypsinogen assay (IRT) and negative for sweat test have formerly been found to carry the major cystic fibrosis (CF) mutation, delta F508, much more frequently than the general population. Among the 716 IRT positive newborns detected by a three tier (IRT, mutation analysis plus meconium lactase assay, sweat test) CF screening programme in north eastern Italy during the period January 1993 to March 1996, we found 45 carriers, a number significantly higher than the expected 17 (p < 0.001). We speculated that some of these heterozygotes could actually be affected by a very mild form of CF, and carry on the other chromosome an undetected CFTR mutation or a DNA variant, such as the 5-thymidine allele in intron 8 of the CFTR gene (IVS8-5T). This hypothesis was tested in four samples; group A (the 45 carriers mentioned above), group B (51 non-carrier, IRT positive neonates), group C (50 IRT negative neonates), and group D (90 CF adult female carriers). Chromosomes with IVS8-5T were seven (7.78%) in group A, seven (6.86%) in group B, five (5%) in group C, and four in group D (2.22%). The 5T prevalence in group A was significantly higher (p < 0.05) compared to group D; similarly, a higher (p < 0.05) 5T frequency in group A compared to group C was detected by considering the chromosomes free from CFTR mutations. This study is consistent with previous papers in finding among neonates with high trypsin levels a CF carrier frequency significantly higher than that expected. It is also suggested that in at least some babies raised trypsin levels at birth could be a phenotypic expression of compound heterozygosity for a major CF mutation plus IVS8-5T.
免疫反应性胰蛋白酶原检测（IRT）呈阳性且汗液检测呈阴性的新生儿，此前已被发现携带主要的囊性纤维化（CF）突变——ΔF508，其频率远高于普通人群。在1993年1月至1996年3月期间，意大利东北部通过三级（IRT、突变分析加胎粪乳糖酶检测、汗液检测）CF筛查项目检测出的716例IRT阳性新生儿中，我们发现了45例携带者，这一数字显著高于预期的17例（p<0.001）。我们推测，这些杂合子中的一些实际上可能受到一种非常轻微形式的CF影响，并且在另一条染色体上携带未检测到的CFTR突变或DNA变异，例如CFTR基因第8内含子中的5 - 胸腺嘧啶等位基因（IVS8 - 5T）。该假设在四个样本中进行了检验；A组（上述45例携带者）、B组（51例非携带者、IRT阳性新生儿）、C组（50例IRT阴性新生儿）和D组（90例成年女性CF携带者）。带有IVS8 - 5T的染色体在A组中有7条（7.78%），B组中有7条（6.86%），C组中有5条（5%），D组中有4条（2.22%）。A组中5T的患病率与D组相比显著更高（p<0.05）；同样，在考虑无CFTR突变的染色体时，A组中5T的频率与C组相比更高（p<0.05）。这项研究与之前的论文一致，即在胰蛋白酶水平高的新生儿中发现CF携带者频率显著高于预期。还表明，至少在一些新生儿中，出生时胰蛋白酶水平升高可能是主要CF突变加IVS8 - 5T的复合杂合性的表型表达。
