Lamzouri Afaf, Ratbi Ilham, Laarabi Fatima Z, Barkat Amina, Sefiani Abdelaziz
Centre de Génomique Humaine, Faculté de Médecine et Pharmacie, Université Mohammed V Souissi, Rabat, Morocco.
Genet Test Mol Biomarkers. 2012 Aug;16(8):996-8. doi: 10.1089/gtmb.2012.0011. Epub 2012 Jul 18.
Frameshift mutation p.G352fsdelG in the PAH gene was recently reported as the most common mutation in Moroccan patients with phenylketonuria (PKU). This result, if confirmed, would considerably facilitate genetic counseling and molecular diagnosis of the disease in Morocco. Given that the incidence of PKU in the Mediterranean region is estimated at between 1/4000 and 1/10,000, this mutation would be harbored by many Moroccans. We aimed to estimate the frequency of heterozygotes for the p.G352fsdelG mutation in Moroccan newborns.
In this study, we used a reliable TaqMan(®) real-time polymerase chain reaction to detect the mutation p.G352fsdelG in the PAH gene in 250 unrelated Moroccan newborns. DNA was extracted from umbilical cord blood with maternal consent.
The supposed recurrent mutation p.G352fsdelG was found in none of the 250 tested newborns. Therefore, the frequency of heterozygotes for this mutation would be less than 1/250, and the incidence of patients with PKU homozygous for this mutation would not exceed 1/100,000.
The p.G352fsdelG mutation in the PAH gene does not appear to be prevalent in the Moroccan population and would be responsible for only few cases of PKU. The previous report of this anomaly as being responsible for 62.5% of PKU patients in Morocco could be explained by selection bias.
最近有报道称，苯丙氨酸羟化酶（PAH）基因中的移码突变p.G352fsdelG是摩洛哥苯丙酮尿症（PKU）患者中最常见的突变。如果这一结果得到证实，将极大地促进摩洛哥该疾病的遗传咨询和分子诊断。鉴于地中海地区PKU的发病率估计在1/4000至1/10000之间，许多摩洛哥人可能携带这种突变。我们旨在估计摩洛哥新生儿中p.G352fsdelG突变杂合子的频率。
在本研究中，我们使用可靠的TaqMan®实时聚合酶链反应检测250名无亲缘关系的摩洛哥新生儿PAH基因中的p.G352fsdelG突变。在获得母亲同意后，从脐带血中提取DNA。
在250名检测的新生儿中均未发现假定的复发性突变p.G352fsdelG。因此，该突变杂合子的频率将低于1/250，该突变纯合的PKU患者发病率不超过1/100000。
PAH基因中的p.G352fsdelG突变在摩洛哥人群中似乎并不普遍，仅导致少数PKU病例。之前关于该异常导致摩洛哥62.5%的PKU患者的报道可能是由选择偏倚造成的。
