A gene for Meckel syndrome maps to chromosome 11q13.
Meckel syndrome (MKS) is a rare autosomal recessive lethal condition of unknown origin, characterized by (i) an occipital meningo-encephalocele with (ii) enlarged kidneys, with multicystic dysplasia and fibrotic changes in the portal area of the liver and with ductal proliferation, and (iii) postaxial polydactyly. A gene responsible for MKS in Finland has been mapped to chromosome 17q21-q24. Studying a subset of Middle Eastern and northern African MKS families, we have recently excluded the chromosome 17 region and have suggested a genetic heterogeneity. In the present study, we report on the mapping of a second MKS locus (MKS2) to chromosome 11q13, by homozygosity mapping in seven families that do not show linkage to chromosome 17q21-q24 (maximum LOD score 4.41 at recombination fraction .01). Most interestingly, the affected fetuses of southern Tunisian ancestry shared a particular haplotype at loci D11S911 and D11S906, suggesting that a founder effect is involved. Our observation gives support to the clinical and genetic heterogeneity of MKS.
Roume
J
J
Unité de Recherches sur les Handicaps Génétiques de lEnfant, INSERMU. 393, France.
Genin
E
E
Cormier-Daire
V
V
Ma
H W
HW
Mehaye
B
B
Attie
T
T
Razavi-Encha
F
F
Fallet-Bianco
C
C
Buenerd
A
A
Clerget-Darpoux
F
F
Munnich
A
A
Le Merrer
M
M
D000015:Abnormalities, Multiple / Q000208:ethnology / Q000235:genetics*; D000352:Africa, Northern / Q000208:ethnology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003241:Consanguinity; D004677:Encephalocele / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008107:Liver Diseases / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D008877:Middle East / Q000208:ethnology; D010375:Pedigree; D017689:Polydactyly / Q000235:genetics
D005819:Genetic Markers