RGD Reference Report - Spectrum of MKS1 and MKS3 mutations in Meckel syndrome: a genotype-phenotype correlation. Mutation in brief #960. Online. - Rat Genome Database

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Spectrum of MKS1 and MKS3 mutations in Meckel syndrome: a genotype-phenotype correlation. Mutation in brief #960. Online.

Authors: Khaddour, R  Smith, U  Baala, L  Martinovic, J  Clavering, D  Shaffiq, R  Ozilou, C  Cullinane, A  Kyttala, M  Shalev, S  Audollent, S  D'Humieres, C  Kadhom, N  Esculpavit, C  Viot, G  Boone, C  Oien, C  Encha-Razavi, F  Batman, PA  Bennett, CP  Woods, CG  Roume, J  Lyonnet, S  Genin, E  Le Merrer, M  Munnich, A  Gubler, MC  Cox, P  MacDonald, F  Vekemans, M  Johnson, CA  Attie-Bitach, T   
Citation: Khaddour R, etal., Hum Mutat. 2007 May;28(5):523-4.
RGD ID: 11063991
Pubmed: PMID:17397051   (View Abstract at PubMed)
DOI: DOI:10.1002/humu.9489   (Journal Full-text)

Meckel syndrome (MKS) is a rare autosomal recessive lethal condition characterized by central nervous system malformations (typically occipital meningoencephalocele), postaxial polydactyly, multicystic kidney dysplasia, and ductal proliferation in the portal area of the liver. MKS is genetically heterogeneous and three loci have been mapped respectively on 17q23 (MKS1), 11q13 (MKS2), and 8q24 (MKS3). Very recently, two genes have been identified: MKS1/FLJ20345 on 17q in Finnish kindreds, carrying the same intronic deletion, c.1408-35_c.1408-7del29, and MKS3/TMEM67 on 8q in families from Pakistan and Oman. Here we report the genotyping of the MKS1 and MKS3 genes in a large, multiethnic cohort of 120 independent cases of MKS. Our first results indicate that the MKS1 and MKS3 genes are each responsible for about 7% of MKS cases with various mutations in different populations. A strong phenotype-genotype correlation, depending on the mutated gene, was observed regarding the type of central nervous system malformation, the frequency of polydactyly, bone dysplasia, and situs inversus. The MKS1 c.1408-35_1408-7del29 intronic mutation was identified in three cases from French or English origin and dated back to 162 generations (approx. 4050 years) ago. We also identified a common MKS3 splice-site mutation, c.1575+1G>A, in five Pakistani sibships of three unrelated families of Mirpuri origin, with an estimated age-of-mutation of 5 generations (125 years).

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Meckel syndrome 1  IAGP 11063991DNA:missense mutations more ...RGD 
Meckel syndrome 1  ISOMKS1 (Homo sapiens)11063991; 11063991DNA:missense mutations more ...RGD 
Meckel syndrome 3  IAGP 11063991DNA:missense mutations and splice-site mutation:exon:multipleRGD 
Meckel syndrome 3  ISOTMEM67 (Homo sapiens)11063991; 11063991DNA:missense mutations and splice-site mutation:exon:multipleRGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cystic renal dysplasia  IAGP 11063991DNA:SNPs and deletions:exons:multipleRGD 
Morphological central nervous system abnormality  IAGP 11063991DNA:SNPs and deletions:exons:multipleRGD 
Objects Annotated

Genes (Rattus norvegicus)
Mks1  (MKS transition zone complex subunit 1)
Tmem67  (transmembrane protein 67)

Genes (Mus musculus)
Mks1  (MKS transition zone complex subunit 1)
Tmem67  (transmembrane protein 67)

Genes (Homo sapiens)
MKS1  (MKS transition zone complex subunit 1)
TMEM67  (transmembrane protein 67)


Additional Information