NDLI: Molecular diagnostics of Meckel–Gruber syndrome highlights phenotypic differences between MKS1 and MKS3

Content Provider	Springer Nature Link
Author	Consugar, Mark B. Kubly, Vickie J. Lager, Donna J. Hommerding, Cynthia J. Wong, Wai Chong Bakker, Egbert Gattone, Vincent H. Torres, Vicente E. Breuning, Martijn H. Harris, Peter C.
Copyright Year	2007
Abstract	Meckel–Gruber syndrome (MKS) is a recessively inherited, lethal disorder characterized by renal cystic dysplasia, occipital encephalocele, polydactyly and biliary dysgenesis. MKS is genetically heterogeneous with three loci mapped and two identified; MKS1 (17q23) and MKS3 (8q22.1). MKS1 is part of the Finnish disease heritage, while MKS3 has been described exclusively in consanguineous Asian families. Here we aimed to establish molecular diagnostics for MKS, determine the importance of MKS1 and MKS3 in non-consanguineous populations, and study genotype/phenotype correlations. The coding regions of MKS1 and MKS3 were screened for mutations by direct sequencing in 17 families clinically diagnosed with MKS in the US or The Netherlands. The clinical phenotype was compared to genic and allelic effects. Both mutations were identified in ten families; five MKS1 and five MKS3. All but two were compound heterozygotes, consistent with their non-consanguineous nature. The MKS1-Finmajor mutation accounted for 7/10 MKS1 mutations; two novel changes were additionally detected. Seven novel mutations were found in MKS3, including three missense changes. We concluded that MKS1 and MKS3 account for the majority of MKS in non-consanguineous populations of European origin. Polydactyly is usually found in MKS1 but rare in MKS3. Cases with no, or milder, CNS phenotypes were only found in MKS3; hypomorphic missense mutations may be associated with less severe CNS outcomes. This study is consistent with further genetic heterogeneity of MKS, but underlines the value of molecular diagnostics of the known genes to aid family planning decisions.
Starting Page	591
Ending Page	599
Page Count	9
File Format	PDF
ISSN	03406717
Journal	Human Genetics
Volume Number	121
Issue Number	5
e-ISSN	14321203
Language	English
Publisher	Springer-Verlag
Publisher Date	2007-03-22
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Meckel syndrome MKS1 MKS3 Molecular diagnostics Genotype/phenotype correlations Metabolic Diseases Internal Medicine Molecular Medicine Human Genetics
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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