A Gene for Meckel Syndrome Maps to Chromosome 11q13

Abstract

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.

Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins

“…The genetic locations of MKSR1 (B9D1; 17p11.2) and MKSR2 (B9D2; 19q13.2d) are clearly outside the uncloned MKS2 locus, which has been mapped to chromosome 11q13 by Roume et al (Roume et al, 1998); thus, MKSR1 and MKSR2 might represent additional disease loci.…”

Normal Ciliogenesis Requires Synergy between the Cystic Kidney Disease Genes MKS-3 and NPHP-4

“…44 Chemotaxis assays to volatile attractants (benzaldehyde) were performed as described previously. 45 Briefly, 10-cm chemotaxis plates containing 2% Difco agar Noble, 5 mM potassium phosphate, pH 6.0, 1 mM CaCl 2 , and 1 mM MgSO 4 were poured 12 to 24 hours before experiments. Plates were marked at the center and at opposite sides, 0.5 cm from the edge.…”

“…The five identified MKS genes encode cilia and/or basal body proteins. [2][3][4][5][6][7] Interestingly, mutations in several of the MKS genes have been found in relatively milder ciliopathies such as nephronophthisis (NPHP), Joubert syndrome (JBTS), and Bardet-Biedl syndrome (BBS). For example, some MKS1 mutations manifest BBS-or NPHP-like phenotypes, and mutations in MKS3 were identified as causing JBTS or NPHP.…”

Spectrum ofMKS1andMKS3mutations in Meckel syndrome: a genotype-phenotype correlation

“…Complete or partial situs inversus and other laterality defects, such as dextrocardia, have been reported in some cases. MKS is genetically heterogeneous and three loci have been mapped on: 17q23 (MKS1) (Paavola, et al, 1995), 11q14 (MKS2) (Roume, et al, 1998), and 8q24 (MKS3) (Morgan, et al, 2002). Very recently, two genes have been identified: MKS1/FLJ20345 (MIM# 609883) on 17q (Kyttälä, et al, 2006) in endogamous Finnish kindreds, and MKS3/TMEM67 (MIM# 607361) on 8q (Smith, et al, 2006) in consanguineous families from Pakistan and Oman.…”