TY - JOUR
T1 - A novel dysmorphic syndrome with open calvarial sutures and sutural cataracts maps to chromosome 14q13-q21
AU - Boyadjiev, Simeon A.
AU - Justice, Cristina M.
AU - Eyaid, Wafaa
AU - McKusick, Victor A.
AU - Lachman, Ralph S.
AU - Chowdry, Arnab B.
AU - Jabak, Monzer
AU - Zwaan, Johan
AU - Wilson, Alexander F.
AU - Jabs, Ethylin Wang
N1 - Funding Information:
Acknowledgements We thank the patients and their family members for their participation. We are grateful to Ahmad Teebi for useful comments on the phenotype, the Al-Habib Medical Center (MCH), Riyadh, Saudi Arabia, for facilitating the clinical and radiological evaluation of the patients, the King Khalid Eye Specialist Hospital for obtaining patient samples and photographs. We thank Laura Kasch-Semenza and William Paznekas for technical assistance. This work was supported by grants NIH T32 GM7471 and K23 DE00462 (S.A.B.) and NIH P60 DE13087, NIH MO1 RR00052, and NIH R01 HD24061 (E.W.J). The genome-wide linkage screen was performed at the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract N01-HG-65403 from the National Institute of Health to the Johns Hopkins University. Some of the results were obtained with the program S.A.G.E., which is supported by grant 1P41 RR03655 from the National Center for Research Resources.
PY - 2003/7
Y1 - 2003/7
N2 - 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 14ql3-q21. The highest LOD scores were obtained for marker GATA136A04 (LOD=4.58 at θ=0.00) and for the adjacent telomeric marker D14S1048 (LOD=4.32 at θ=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 14ql3-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.
AB - 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 14ql3-q21. The highest LOD scores were obtained for marker GATA136A04 (LOD=4.58 at θ=0.00) and for the adjacent telomeric marker D14S1048 (LOD=4.32 at θ=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 14ql3-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.
UR - https://www.scopus.com/pages/publications/0037559311
U2 - 10.1007/s00439-003-0932-6
DO - 10.1007/s00439-003-0932-6
M3 - Article
C2 - 12677423
AN - SCOPUS:0037559311
SN - 0340-6717
VL - 113
SP - 1
EP - 9
JO - Human Genetics
JF - Human Genetics
IS - 1
ER -