Editor—Silver-Russell syndrome (SRS) describes a uniform malformation syndrome characterised by intrauterine and postnatal growth retardation (IUGR/PGR), asymmetry of the head and limbs, a small triangular face, and other less constant features. The majority of the 400 cases described so far occurred sporadically, but some familial cases indicate a genetic cause of the disease. In rare cases, chromosomal aberrations have been found. Although no uniform pattern is apparent,1 five cases have recently been reported involving chromosome 7.2-6 A subset of 7-10% of SRS patients shows maternal uniparental disomy (mUPD) for the whole of chromosome 7,7 thus indicating the involvement of at least one imprinted gene on this chromosome. Mutations in this gene or imprinting mutations may contribute to the SRS phenotype. So far, two imprinted genes localised in 7q32 (MEST/PEG1,COP-G2) have been excluded as candidate genes for SRS.8 9

PAX4 is a member of a highly conserved gene family,10 and has been mapped to 7q32.11Evidence of the crucial role of PAX genes in organogenesis and in differentiation is provided by mouse developmental mutants12 as well as by human diseases (PAX2, kidney abnormalities, optic nerve coloboma; PAX3, Waardenburg syndrome types I and III; PAX5, small lymphotic lymphomas;PAX6, aniridia;PAX9, optic nerve coloboma).10 13 14

A role for PAX4 in the aetiology of diabetes type II has recently been dismissed by investigations in a group of French patients as well as in a population of 116 unrelated Ashkenazi Jews affected by the disease.15 16 Furthermore,PAX4 has been ruled out as a possible candidate gene for the Wolcott-Rallison syndrome.17

The PAX4 gene product contains two DNA binding motifs, a paired domain which consists of three alpha helices, and a paired …