LINKAGE OF BLEPHAROPHIMOSIS SYNDROME IN A LARGE INDIAN PEDIGREE TO CHROMOSOME 7P

Blepharophimosis syndrome (BPES) is an autosomal dominant disorder inv olving abnormal eyelid development, Cytogenetic and linkage analyses h ave previously implicated the chromosome 3q23 region in multiple cases of this syndrome. However, in a few cases cytogenetic analyses have i mplicated other chromosomal regions in this condition, Here we report linkage of BPES in a large Indian pedigree to chromosome 7p13-p21; aff ected only two-point and multipoint analyses using D7S488, D7S2551 and D7S2562 both showed peak lod scores of 3.61 coincident with D7S2562, Recombinations in affected individuals placed the critical region betw een D7S488 and D7S629, When both affected and unaffected individuals w ere considered, a maximum two-point lod score of 3.38 at theta = 0.08 was obtained with D7S2551 while a peak multipoint lod score of 3.64 wa s obtained between D7S488 and D7S2551, Segregation analysis revealed t wo unaffected individuals carrying the affected haplotype accounted fo r the difference in peak, relative to the affected only analysis. The chromosome 7p candidate genes inhibin beta A and epidermal growth fact or receptor map outside this region whereas the HOX1 gene cluster may map inside this region, Although BPES is sometimes associated with fem ale infertility due to premature ovarian failure, in the current famil y affected females were fertile, The current finding together with the previous evidence implicating chromosome 3q2 provides strong evidence that BPES involves locus heterogeneity; this point should be consider ed when counselling affected families.