title: A novel dysmorphic syndrome with open calvarial sutures and sutural cataracts maps to chromosome 14q13-q21.
abstract: We describe a new dysmorphic syndrome in an inbred Saudi Arabian family with 21 members. Five males and one female have similar craniofacial features including wide open calvarial sutures with large and late-closing anterior fontanels, frontal bossing, hyperpigmentation with capillary hemangioma of the forehead, significant hypertelorism, and a broad and prominent nose. In addition, these individuals have Y-shaped sutural cataracts diagnosed by 1-2 years of age. No chromosomal or biochemical abnormalities were identified. A genome-wide scan was performed, and two-point LOD score analysis, assuming autosomal recessive inheritance, detected linkage to chromosome 14q13-q21. The highest LOD scores were obtained for marker GATA136A04 (LOD=4.58 at theta=0.00) and for the adjacent telomeric marker D14S1048 (LOD=4.32 at theta=0.00). Multipoint linkage analysis resulted in a maximum LOD score of 5.44 between markers D14S1048 and GATA136A04. Model independent analysis by SIBPAL confirmed linkage to the same chromosomal region. Haplotype analysis indicated that all affected individuals were homozygous for the interval on chromosome 14q13-q21 with two recombinants for D14S1014 (centromeric) and one recombinant for D14S301 (telomeric). These recombinations limit the disease locus to a region of approximately 7.26 Mb. Candidate genes localized to this region were identified, and analysis of PAX9 did not identify mutations in these patients. The unique clinical phenotype and the mapping data suggest that this family represents a novel autosomal recessive syndrome.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Center for Craniofacial Development and Disorders, Department of Pediatrics, The Johns Hopkins University School of Medicine, MD 21287-3914, Baltimore, USA. sboyd@mail.jhmi.edu
authors.forename: Simeon A
authors.initials: SA
authors.lastname: Boyadjiev
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Justice
authors.forename: Wafaa
authors.initials: W
authors.lastname: Eyaid
authors.forename: Victor A
authors.initials: VA
authors.lastname: McKusick
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Lachman
authors.forename: Arnab B
authors.initials: AB
authors.lastname: Chowdry
authors.forename: Monzer
authors.initials: M
authors.lastname: Jabak
authors.forename: Johan
authors.initials: J
authors.lastname: Zwaan
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Wilson
authors.forename: Ethylin Wang
authors.initials: EW
authors.lastname: Jabs
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D003393:Cranial Sutures / Q000002:abnormalities*; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D012529:Saudi Arabia; D013577:Syndrome