BACKGROUND: EEM syndrome is the rare association of ectodermal dysplasia, 
ectrodactyly, and macular dystrophy.
METHODS: We here demonstrate through molecular analysis that EEM is caused by 
distinct homozygous CDH3 mutations in two previously published families.
RESULTS: In family 1, a missense mutation (c.965A-->T) causes a change of amino 
acid 322 from asparagine to isoleucine; this amino acid is located in a highly 
conserved motif likely to affect Ca2+ binding affecting specificity of the 
cell-cell binding function. In family 2, a homozygous frameshift deletion 
(c.829delG) introduces a truncated fusion protein with a premature stop codon at 
amino acid residue 295, expected to cause a non-functional protein lacking both 
its intracellular and membrane spanning domains and its extracellular cadherin 
repeats 3-5. Our mouse in situ expression data demonstrate that Cdh3 is 
expressed in the apical ectodermal ridge from E10.5 to E12.5, and later in the 
interdigital mesenchyme, a pattern compatible with the EEM phenotype. 
Furthermore, we discuss possible explanations for the phenotypic differences 
between EEM and congenital hypotrichosis with juvenile macular dystrophy (HJMD), 
which is also caused by CDH3 mutations.
CONCLUSIONS: In summary, we have ascertained a third gene associated with 
ectrodactyly and have demonstrated a hitherto unrecognised role of CDH3 in 
shaping the human hand.