Genetic heterogeneity of syndromic X-linked recessive microphthalmia-anophthalmia: is Lenz microphthalmia a single disorder?
Nonsyndromic congenital microphthalmia or anophthalmia is a heterogeneous malformation with autosomal dominant, autosomal recessive, and X-linked modes of inheritance. Lenz microphthalmia syndrome comprises microphthalmia with mental retardation, malformed ears, skeletal anomalies, and is inherited in an X-linked recessive pattern. Prior studies have shown linkage of both isolated (or nonsyndromic) anophthalmos (ANOP1, [MIM 301590]) and Lenz syndrome [MIM 309800] to Xq27-q28. Nonsyndromic colobomatous microphthalmia [MIM 300345] has been linked to Xp11.4-Xq11.1. We describe a five-generation African-American family with microphthalmia or anophthalmia, mental retardation, and urogenital anomalies, in an X-linked recessive inheritance pattern, consistent with Lenz syndrome. Initial linkage analysis with microsatellite markers excluded the region in Xq27-q28 previously reported as a candidate region for ANOP1 [MIM 301590]. An X-chromosome scan revealed linkage to a 10-cM region between markers DXS228 and DXS992 in Xp11.4-p21.2. Multipoint analysis gave a maximum LOD score of 2.46 at marker DXS993. These data show that X-linked recessive syndromic microphthalmia exhibits genetic heterogeneity. In addition, it suggests that Lenz microphthalmia syndrome, previously thought to be a single disorder, may represent an amalgam of two distinct disorders.
Medical Genetics Branch, NHGRI, National Institutes of Health, Bethesda, Maryland 20892-4472, USA. davidng@nhgri.nih.gov
David
D
Ng
Donald W
DW
Hadley
Cynthia J
CJ
Tifft
Leslie G
LG
Biesecker
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000853:Anophthalmos / Q000150:complications / Q000235:genetics*; D019465:Craniofacial Abnormalities; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive / Q000235:genetics; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D008850:Microphthalmos / Q000150:complications / Q000235:genetics*; D018895:Microsatellite Repeats; D010375:Pedigree; D013577:Syndrome; D014960:X Chromosome / Q000235:genetics*