Amiel J, Audollent S, Joly D, Dureau P, Salomon R, Tellier A L, Augé J, Bouissou F, Antignac C, Gubler M C, Eccles M R, Munnich A, Vekemans M, Lyonnet S, Attié-Bitach T
Département de Génétique et Unité INSERM U-393, Paris, France.
Eur J Hum Genet. 2000 Nov;8(11):820-6. doi: 10.1038/sj.ejhg.5200539.
The renal-coloboma syndrome (RCS, MIM 120330) is an autosomal dominant disorder caused by PAX2 gene mutations. We screened the entire coding sequence of the PAX2 gene for mutations in nine patients with RCS. We found five heterozygous PAX2 gene mutations: a dinucleotide insertion (2G) at position 619 in one sporadic RCS case, a single nucleotide insertion (619 + G) in three unrelated cases, and a single nucleotide deletion in a familial case. In this familial case, three affected sibs showed a striking ocular phenotypic variability. Each of the sibs carried a 619insG mutation, whilst unaffected parents did not, suggesting the presence of germline mosaicism. Interestingly, the 619insG mutation has been previously reported in several patients and is also responsible for the Pax21Neu mouse mutant, an animal model of human RCS. This study confirms the critical role of the PAX2 gene in human renal and ocular development. In addition, it emphasises the high variability of ocular defects associated with PAX2 mutations ranging from subtle optic disc anomalies to microphthalmia. Finally, the presence of PAX2 germline mosaicism highlights the difficulties associated with genetic counselling for PAX2 mutations.
肾-眼裂综合征（RCS，MIM 120330）是一种由PAX2基因突变引起的常染色体显性遗传病。我们对9例RCS患者的PAX2基因整个编码序列进行了突变筛查。我们发现了5种PAX2基因杂合突变：1例散发型RCS病例中第619位的二核苷酸插入（2G），3例无亲缘关系病例中的单核苷酸插入（619 + G），以及1例家族性病例中的单核苷酸缺失。在该家族性病例中，3名患病同胞表现出显著的眼部表型变异性。每个同胞都携带619insG突变，而未患病的父母则没有，这表明存在生殖系嵌合体。有趣的是，先前在数名患者中已报道过619insG突变，它也是人类RCS动物模型Pax21Neu小鼠突变体的致病原因。本研究证实了PAX2基因在人类肾脏和眼部发育中的关键作用。此外，它强调了与PAX2突变相关的眼部缺陷的高度变异性，范围从细微的视盘异常到小眼症。最后，PAX2生殖系嵌合体的存在突出了PAX2突变遗传咨询的困难。
