Localisation of a gene for an autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia, and distinctive facies to chromosome 15q26.
BACKGROUND
We have previously described an autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia (MED), and distinctive facies in a large, extended Omani family. The MED observed seems to be part of a larger malformation syndrome, since both craniofacial and central nervous system changes were present in the family. We performed a whole genome scan in this family in order to identify the gene locus for this malformation syndrome.


RESULTS
Using homozygosity mapping, we show linkage to the telomeric region of the long arm of chromosome 15. The position of both the disease gene and the principal glycoprotein, chondroitin sulphate proteoglycan (aggrecan, AGC1) on chromosome 15q26, suggested that the aggrecan gene is a candidate for the disease in this family. However, three of the four affected children were heterozygous for a polymorphism at position 831 of the coding sequence of AGC1, providing strong evidence against its involvement.


CONCLUSIONS
We have identified a gene locus for a recessive syndrome of macrocephaly, MED, and distinctive facies in a large Omani family. Aggrecan located on chromosome 15q26, within the critical region determined for this syndrome in this family, was excluded as a candidate gene.
Bayoumi
R
R
Department of Biochemistry, College of Medicine, Sultan Qaboos University, Muscat, Sultanate of Oman.
Saar
K
K
Lee
Y A
YA
Nürnberg
G
G
Reis
A
A
Nur-E-Kamal
M
M
Al-Gazali
L I
LI
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D053674:Aggrecans; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D003241:Consanguinity; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D016326:Extracellular Matrix Proteins; D019066:Facies; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011509:Proteoglycans / Q000235:genetics; D011859:Radiography; D013577:Syndrome
C508319:ACAN protein, human; D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans