Genetic mapping of a novel X-linked recessive colobomatous microphthalmia

Colobomatous microphthalmia is a common ocular malformation with a heteroge neous phenotype, The majority of cases without associated systemic abnormal ities have an autosomal dominant inheritance pattern [McKusick, 1990: Mende lian inheritance in man], A few isolated cases with autosomal recessive tra nsmission have been described [Zlotogora ct al,, 1994: Am J Med Genet 49:26 1-262]. To our knowledge, no cases of X-linked colobomatous microphthalmia that are not a part of a syndrome or a multisystem disorder have been repor ted. In this study, we describe a genetic and clinical evaluation of a larg e pedigree in which colobomatous microphthalmia is segregating in an X-link ed recessive fashion. Based on recombination breakpoint analysis, we have d etermined that the critical interval exists between markers DXS989 and DXS4 41, placing the disease locus on the proximal short arm or the proximal lon g arm of the X chromosome. Using linkage analysis, we obtained two-point lo d scores of 2.71 at zero recombination with markers DXS1058, DXS6810, DXS11 99, and DXS7132, Overlapping multipoint analysis established a broad maximu m from marker DXS1068 to marker DXS7132, a region spanning approximately 28 cM. This study provides evidence for the presence of a new locus for colob omatous microphthalmia. (C) 2001 Wiley-Liss, Inc.