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Article: A novel missense mutation in the galactosyltransferase-I (B4GALT7) gene in a family exhibiting facioskeletal anomalies and Ehlers-Danlos syndrome resembling the progeroid type

TitleA novel missense mutation in the galactosyltransferase-I (B4GALT7) gene in a family exhibiting facioskeletal anomalies and Ehlers-Danlos syndrome resembling the progeroid type
Authors
KeywordsAutosomal recessive
B4GALT7 mutation
Connective tissue disorders
Facioskeletal type of EDS
Progeroid-like phenotype
Issue Date2004
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jabout/33129/ProductInformation.html
Citation
American Journal Of Medical Genetics, 2004, v. 128 A n. 1, p. 39-45 How to Cite?
AbstractThe Ehlers-Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. Several genes have been implicated to result in EDS phenotypes. The progeroid type of EDS is characterized by wrinkled, loose skin on the face, curly fine hair, scanty eyebrows and eyelashes, in addition to the classical features of EDS. Here we describe two similarly affected individuals in two sibships of a large consanguineous family from Qatar. DNA samples from affected and unaffected members of the family were analyzed for homozygosity of polymorphic markers associated with genes that have been implicated in EDS. Among 28 markers analyzed, homozygosity was only observed for D5S469 and D5S2111, which were markers for galactosyltransferase-I (B4GALT7) located on chromosome 5q35.2, where the previously reported progeroid-like variant of EDS has been mapped. Exons harboring the coding regions and exon-intron junctions of B4GALT7 were amplified by PCR and examined for mutations. A homozygous misssense C to T substitution at nucleotide 808 in the coding region was discovered in both affected individuals. The carrier parents were heterozygous for this mutation, which was not found among 76 DNA samples from control individuals of the same ethnicity. Segregation of this novel mutation in the family further confirmed the allelic variant and its recessive mode of inheritance in this type of EDS. The C to T substitution results in an arginine to cysteine change at amino acid residue 270 that is located in the catalytically active extracellular C-terminal domain. This change could result in abnormal protein folding and/or aberrant interactions of mutated galactosyltransferase-I with other extracellular matrix proteins leading to the development of a progeroid-like phenotype in affected individuals. © 2004 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/44388
ISSN
2015 Impact Factor: 2.082
2015 SCImago Journal Rankings: 1.115
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorFaiyazUlHaque, Men_HK
dc.contributor.authorZaidi, SHEen_HK
dc.contributor.authorAlAli, Men_HK
dc.contributor.authorAlMureikhi, MSen_HK
dc.contributor.authorKennedy, Sen_HK
dc.contributor.authorAlThani, Gen_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorTeebi, ASen_HK
dc.date.accessioned2007-09-12T03:52:35Z-
dc.date.available2007-09-12T03:52:35Z-
dc.date.issued2004en_HK
dc.identifier.citationAmerican Journal Of Medical Genetics, 2004, v. 128 A n. 1, p. 39-45en_HK
dc.identifier.issn1552-4825en_HK
dc.identifier.urihttp://hdl.handle.net/10722/44388-
dc.description.abstractThe Ehlers-Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. Several genes have been implicated to result in EDS phenotypes. The progeroid type of EDS is characterized by wrinkled, loose skin on the face, curly fine hair, scanty eyebrows and eyelashes, in addition to the classical features of EDS. Here we describe two similarly affected individuals in two sibships of a large consanguineous family from Qatar. DNA samples from affected and unaffected members of the family were analyzed for homozygosity of polymorphic markers associated with genes that have been implicated in EDS. Among 28 markers analyzed, homozygosity was only observed for D5S469 and D5S2111, which were markers for galactosyltransferase-I (B4GALT7) located on chromosome 5q35.2, where the previously reported progeroid-like variant of EDS has been mapped. Exons harboring the coding regions and exon-intron junctions of B4GALT7 were amplified by PCR and examined for mutations. A homozygous misssense C to T substitution at nucleotide 808 in the coding region was discovered in both affected individuals. The carrier parents were heterozygous for this mutation, which was not found among 76 DNA samples from control individuals of the same ethnicity. Segregation of this novel mutation in the family further confirmed the allelic variant and its recessive mode of inheritance in this type of EDS. The C to T substitution results in an arginine to cysteine change at amino acid residue 270 that is located in the catalytically active extracellular C-terminal domain. This change could result in abnormal protein folding and/or aberrant interactions of mutated galactosyltransferase-I with other extracellular matrix proteins leading to the development of a progeroid-like phenotype in affected individuals. © 2004 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jabout/33129/ProductInformation.htmlen_HK
dc.relation.ispartofAmerican Journal of Medical Geneticsen_HK
dc.subjectAutosomal recessiveen_HK
dc.subjectB4GALT7 mutationen_HK
dc.subjectConnective tissue disordersen_HK
dc.subjectFacioskeletal type of EDSen_HK
dc.subjectProgeroid-like phenotypeen_HK
dc.subject.meshB4galt7 mutationen_HK
dc.subject.meshFacioskeletal type of edsen_HK
dc.subject.meshAutosomal recessiveen_HK
dc.subject.meshConnective tissue disordersen_HK
dc.subject.meshProgeroid-like phenotypen_HK
dc.titleA novel missense mutation in the galactosyltransferase-I (B4GALT7) gene in a family exhibiting facioskeletal anomalies and Ehlers-Danlos syndrome resembling the progeroid typeen_HK
dc.typeArticleen_HK
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturelink_to_subscribed_fulltexten_HK
dc.identifier.doi10.1002/ajmg.a.30005en_HK
dc.identifier.pmid15211654-
dc.identifier.scopuseid_2-s2.0-3042846793en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-3042846793&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume128 Aen_HK
dc.identifier.issue1en_HK
dc.identifier.spage39en_HK
dc.identifier.epage45en_HK
dc.identifier.isiWOS:000222329000009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridFaiyazUlHaque, M=6603280179en_HK
dc.identifier.scopusauthoridZaidi, SHE=7101670271en_HK
dc.identifier.scopusauthoridAlAli, M=55175797600en_HK
dc.identifier.scopusauthoridAlMureikhi, MS=6503930036en_HK
dc.identifier.scopusauthoridKennedy, S=7401494096en_HK
dc.identifier.scopusauthoridAlThani, G=6505789694en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridTeebi, AS=7004661664en_HK

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