Mutation analysis in the candidate Möbius syndrome genes PGT and GATA2 on chromosome 3 and EGR2 on chromosome 10

Mobius syndrome (MBS, MIM 157900) is a rare congenital disorder characterised by paralysis of the facial nerve. This paralysis may be complete or partial and unilateral or bilateral. Other cranial nerves are often implicated, most frequently the abducens and hypoglossal nerve. Limb malformations and facial dysmorphism occur frequently. Features seen less often in MBS are structural anomalies of the ear, defective branchial musculature (Poland syndrome, MIM 173800), and mild mental retardation.1 Although Mobius syndrome usually occurs in isolated cases, familial recurrence has been reported. Patterns of inheritance observed in affected families suggest different modes of inheritance for the syndrome, ranging from autosomal recessive to autosomal dominant and X linked. To date, four genetic loci for MBS have been described. In 1977, a reciprocal translocation of 13q12.2-13 was identified, cosegregating with the disease in a three generation MBS family.2 Slee et al 3 reported a MBS patient with a deletion of chromosome 13q12.2 in 1991. Therefore, chromosome 13q12.2-q13 is thought to harbour a gene for MBS (MBS1). We identified two additional loci for MBS, MBS2 at 3q21-q224 and MBS3 at 10q21,1 in two large Dutch families with a mild Mobius phenotype, cosegregating in an autosomal dominant fashion with reduced penetrance. A fourth locus harbouring a gene for MBS on chromosome 1p22 was inferred from two reports. Donahue et al 5 identified a t(1;11)(p22;p13) translocation in a patient with Mobius syndrome. The 1p22 locus was confirmed by a t(1;2)(p22.3;q21.1) translocation in a patient with …