A Locus for Autosomal Recessive Congenital Microphthalmia Maps to Chromosome 14q32

• Published in: American journal of human genetics Vol. 62; no. 5; pp. 1113 - 1116
• Main Authors: Bessant, David A.R., Khaliq, Shagufta, Hameed, Abdul, Anwar, Khalid, Mehdi, S. Qasim, Payne, Annette M., Bhattacharya, Shomi S.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01-05-1998; University of Chicago Press
• Subjects: Animals; Biological and medical sciences; Child; Chromosome Mapping; Chromosomes, Human, Pair 14; Eye development; Female; Genes, Recessive; Genetics; Humans; Linkage analysis; Male; Malformations of the eye; Medical sciences; Mice; Microphthalmia; Microphthalmos - genetics; Ophthalmology; Pedigree; Polymorphism, Genetic; Recombination, Genetic; Genetics; Eye development; Microphthalmia; Linkage analysis; Genetic mapping; Human; Linkage; Family study; Chromosome D14; Homozygosity; Congenital disease; Genetic determinism; Genetic disease; Eye disease; Gene; Malformation; Autosomal character; Recessive character; Consanguinity; Locus
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/301843

Congenital microphthalmia (CMIC) (OMIM
309700) may occur in isolation or in association with a variety of systemic malformations. Isolated CMIC may be inherited as an autosomal dominant, an autosomal recessive, or an X-linked trait. On the basis of a whole-genome linkage analysis, we have mapped the first locus for isolated CMIC, in a five-generation consanguineous family with autosomal recessive inheritance, to chromosome 14q32. All affected individuals in this family have bilateral CMIC. Linkage analysis gave a maximum two-point LOD score of 3.55 for the marker D14S65. Surrounding this marker is a region of homozygosity of 7.3 cM, between the markers D14S987 and D14S267, within which the disease gene is predicted to lie. The genes for several eye-specific transcription factors are located on human chromosome 14q and in the syntenic region of mouse chromosome 12. However, both
CHX10 (14q24.3), mutations of which give rise to CMIC in mouse models, and
OTX2 (14q21–22) can be excluded as candidates for autosomal recessive congenital microphthalmia (arCMIC), since they map outside the critical disease region defined by recombination events. This suggests that arCMIC is caused by defects in a novel developmental gene that may be important or even essential in eye development.