Homozygosity for Frameshift Mutations in XYLT2 Result in a Spondylo-Ocular Syndrome with Bone Fragility, Cataracts, and Hearing Defects
Identifieur interne : 001D09 ( Main/Merge ); précédent : 001D08; suivant : 001D10Homozygosity for Frameshift Mutations in XYLT2 Result in a Spondylo-Ocular Syndrome with Bone Fragility, Cataracts, and Hearing Defects
Auteurs : Craig F. Munns [Australie] ; Somayyeh Fahiminiya [Canada] ; Nabin Poudel [États-Unis] ; Maria Cristina Munteanu [États-Unis] ; Jacek Majewski [Canada] ; David O. Sillence [Australie] ; Jordan P. Metcalf [États-Unis] ; Andrew Biggin [Australie] ; Francis Glorieux [Canada] ; François Fassier [Canada] ; Frank Rauch [Canada] ; Myron E. Hinsdale [États-Unis]Source :
- American Journal of Human Genetics [ 0002-9297 ] ; 2015.
Abstract
Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular and tissue homeostasis including growth factor function, morphogen gradient formation, and co-receptor activity. Proteoglycan assembly initiates with a xylose monosaccharide covalently attached by either xylosyltransferase I or II. Three individuals from two families were found that exhibited similar phenotypes. The index case subjects were two brothers, individuals 1 and 2, who presented with osteoporosis, cataracts, sensorineural hearing loss, and mild learning defects. Whole exome sequence analyses showed that both individuals had a homozygous c.692dup mutation (GenBank:
Url:
DOI: 10.1016/j.ajhg.2015.04.017
PubMed: 26027496
PubMed Central: 4457947
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 001E58
- to stream Pmc, to step Curation: 001E57
- to stream Pmc, to step Checkpoint: 001198
- to stream Ncbi, to step Merge: 007440
- to stream Ncbi, to step Curation: 007440
- to stream Ncbi, to step Checkpoint: 007440
Links to Exploration step
PMC:4457947Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Homozygosity for Frameshift Mutations in <italic>XYLT2</italic>
Result in a Spondylo-Ocular Syndrome with Bone Fragility, Cataracts, and Hearing Defects</title>
<author><name sortKey="Munns, Craig F" sort="Munns, Craig F" uniqKey="Munns C" first="Craig F." last="Munns">Craig F. Munns</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145</wicri:regionArea>
<wicri:noRegion>NSW 2145</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fahiminiya, Somayyeh" sort="Fahiminiya, Somayyeh" uniqKey="Fahiminiya S" first="Somayyeh" last="Fahiminiya">Somayyeh Fahiminiya</name>
<affiliation wicri:level="1"><nlm:aff id="aff2">Department of Human Genetics, Faculty of Medicine, McGill University and Genome Quebec Innovation Center, Montréal, QC H3A 1B1, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Human Genetics, Faculty of Medicine, McGill University and Genome Quebec Innovation Center, Montréal, QC H3A 1B1</wicri:regionArea>
<wicri:noRegion>QC H3A 1B1</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Poudel, Nabin" sort="Poudel, Nabin" uniqKey="Poudel N" first="Nabin" last="Poudel">Nabin Poudel</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078</wicri:regionArea>
<wicri:noRegion>OK 74078</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Munteanu, Maria Cristina" sort="Munteanu, Maria Cristina" uniqKey="Munteanu M" first="Maria Cristina" last="Munteanu">Maria Cristina Munteanu</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078</wicri:regionArea>
<wicri:noRegion>OK 74078</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Majewski, Jacek" sort="Majewski, Jacek" uniqKey="Majewski J" first="Jacek" last="Majewski">Jacek Majewski</name>
<affiliation wicri:level="1"><nlm:aff id="aff2">Department of Human Genetics, Faculty of Medicine, McGill University and Genome Quebec Innovation Center, Montréal, QC H3A 1B1, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Human Genetics, Faculty of Medicine, McGill University and Genome Quebec Innovation Center, Montréal, QC H3A 1B1</wicri:regionArea>
<wicri:noRegion>QC H3A 1B1</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sillence, David O" sort="Sillence, David O" uniqKey="Sillence D" first="David O." last="Sillence">David O. Sillence</name>
<affiliation wicri:level="1"><nlm:aff id="aff4">Discipline of Genetic Medicine, The Children’s Hospital at Westmead Clinical School, Sydney Medicine, Westmead, NSW 2145, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Discipline of Genetic Medicine, The Children’s Hospital at Westmead Clinical School, Sydney Medicine, Westmead, NSW 2145</wicri:regionArea>
<wicri:noRegion>NSW 2145</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Metcalf, Jordan P" sort="Metcalf, Jordan P" uniqKey="Metcalf J" first="Jordan P." last="Metcalf">Jordan P. Metcalf</name>
<affiliation wicri:level="1"><nlm:aff id="aff5">Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126</wicri:regionArea>
<wicri:noRegion>OK 73126</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Biggin, Andrew" sort="Biggin, Andrew" uniqKey="Biggin A" first="Andrew" last="Biggin">Andrew Biggin</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145</wicri:regionArea>
<wicri:noRegion>NSW 2145</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Glorieux, Francis" sort="Glorieux, Francis" uniqKey="Glorieux F" first="Francis" last="Glorieux">Francis Glorieux</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Shriners Hospital for Children, Montréal, QC H3G 1A6, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Shriners Hospital for Children, Montréal, QC H3G 1A6</wicri:regionArea>
<wicri:noRegion>QC H3G 1A6</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fassier, Francois" sort="Fassier, Francois" uniqKey="Fassier F" first="François" last="Fassier">François Fassier</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Shriners Hospital for Children, Montréal, QC H3G 1A6, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Shriners Hospital for Children, Montréal, QC H3G 1A6</wicri:regionArea>
<wicri:noRegion>QC H3G 1A6</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Rauch, Frank" sort="Rauch, Frank" uniqKey="Rauch F" first="Frank" last="Rauch">Frank Rauch</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Shriners Hospital for Children, Montréal, QC H3G 1A6, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Shriners Hospital for Children, Montréal, QC H3G 1A6</wicri:regionArea>
<wicri:noRegion>QC H3G 1A6</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hinsdale, Myron E" sort="Hinsdale, Myron E" uniqKey="Hinsdale M" first="Myron E." last="Hinsdale">Myron E. Hinsdale</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078</wicri:regionArea>
<wicri:noRegion>OK 74078</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff7">Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126</wicri:regionArea>
<wicri:noRegion>OK 73126</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">26027496</idno>
<idno type="pmc">4457947</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457947</idno>
<idno type="RBID">PMC:4457947</idno>
<idno type="doi">10.1016/j.ajhg.2015.04.017</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">001E58</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E58</idno>
<idno type="wicri:Area/Pmc/Curation">001E57</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001E57</idno>
<idno type="wicri:Area/Pmc/Checkpoint">001198</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001198</idno>
<idno type="wicri:Area/Ncbi/Merge">007440</idno>
<idno type="wicri:Area/Ncbi/Curation">007440</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">007440</idno>
<idno type="wicri:doubleKey">0002-9297:2015:Munns C:homozygosity:for:frameshift</idno>
<idno type="wicri:Area/Main/Merge">001D09</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Homozygosity for Frameshift Mutations in <italic>XYLT2</italic>
Result in a Spondylo-Ocular Syndrome with Bone Fragility, Cataracts, and Hearing Defects</title>
<author><name sortKey="Munns, Craig F" sort="Munns, Craig F" uniqKey="Munns C" first="Craig F." last="Munns">Craig F. Munns</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145</wicri:regionArea>
<wicri:noRegion>NSW 2145</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fahiminiya, Somayyeh" sort="Fahiminiya, Somayyeh" uniqKey="Fahiminiya S" first="Somayyeh" last="Fahiminiya">Somayyeh Fahiminiya</name>
<affiliation wicri:level="1"><nlm:aff id="aff2">Department of Human Genetics, Faculty of Medicine, McGill University and Genome Quebec Innovation Center, Montréal, QC H3A 1B1, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Human Genetics, Faculty of Medicine, McGill University and Genome Quebec Innovation Center, Montréal, QC H3A 1B1</wicri:regionArea>
<wicri:noRegion>QC H3A 1B1</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Poudel, Nabin" sort="Poudel, Nabin" uniqKey="Poudel N" first="Nabin" last="Poudel">Nabin Poudel</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078</wicri:regionArea>
<wicri:noRegion>OK 74078</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Munteanu, Maria Cristina" sort="Munteanu, Maria Cristina" uniqKey="Munteanu M" first="Maria Cristina" last="Munteanu">Maria Cristina Munteanu</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078</wicri:regionArea>
<wicri:noRegion>OK 74078</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Majewski, Jacek" sort="Majewski, Jacek" uniqKey="Majewski J" first="Jacek" last="Majewski">Jacek Majewski</name>
<affiliation wicri:level="1"><nlm:aff id="aff2">Department of Human Genetics, Faculty of Medicine, McGill University and Genome Quebec Innovation Center, Montréal, QC H3A 1B1, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Human Genetics, Faculty of Medicine, McGill University and Genome Quebec Innovation Center, Montréal, QC H3A 1B1</wicri:regionArea>
<wicri:noRegion>QC H3A 1B1</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sillence, David O" sort="Sillence, David O" uniqKey="Sillence D" first="David O." last="Sillence">David O. Sillence</name>
<affiliation wicri:level="1"><nlm:aff id="aff4">Discipline of Genetic Medicine, The Children’s Hospital at Westmead Clinical School, Sydney Medicine, Westmead, NSW 2145, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Discipline of Genetic Medicine, The Children’s Hospital at Westmead Clinical School, Sydney Medicine, Westmead, NSW 2145</wicri:regionArea>
<wicri:noRegion>NSW 2145</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Metcalf, Jordan P" sort="Metcalf, Jordan P" uniqKey="Metcalf J" first="Jordan P." last="Metcalf">Jordan P. Metcalf</name>
<affiliation wicri:level="1"><nlm:aff id="aff5">Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126</wicri:regionArea>
<wicri:noRegion>OK 73126</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Biggin, Andrew" sort="Biggin, Andrew" uniqKey="Biggin A" first="Andrew" last="Biggin">Andrew Biggin</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145</wicri:regionArea>
<wicri:noRegion>NSW 2145</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Glorieux, Francis" sort="Glorieux, Francis" uniqKey="Glorieux F" first="Francis" last="Glorieux">Francis Glorieux</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Shriners Hospital for Children, Montréal, QC H3G 1A6, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Shriners Hospital for Children, Montréal, QC H3G 1A6</wicri:regionArea>
<wicri:noRegion>QC H3G 1A6</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fassier, Francois" sort="Fassier, Francois" uniqKey="Fassier F" first="François" last="Fassier">François Fassier</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Shriners Hospital for Children, Montréal, QC H3G 1A6, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Shriners Hospital for Children, Montréal, QC H3G 1A6</wicri:regionArea>
<wicri:noRegion>QC H3G 1A6</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Rauch, Frank" sort="Rauch, Frank" uniqKey="Rauch F" first="Frank" last="Rauch">Frank Rauch</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Shriners Hospital for Children, Montréal, QC H3G 1A6, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Shriners Hospital for Children, Montréal, QC H3G 1A6</wicri:regionArea>
<wicri:noRegion>QC H3G 1A6</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hinsdale, Myron E" sort="Hinsdale, Myron E" uniqKey="Hinsdale M" first="Myron E." last="Hinsdale">Myron E. Hinsdale</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078</wicri:regionArea>
<wicri:noRegion>OK 74078</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff7">Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126</wicri:regionArea>
<wicri:noRegion>OK 73126</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">American Journal of Human Genetics</title>
<idno type="ISSN">0002-9297</idno>
<idno type="eISSN">1537-6605</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular and tissue homeostasis including growth factor function, morphogen gradient formation, and co-receptor activity. Proteoglycan assembly initiates with a xylose monosaccharide covalently attached by either xylosyltransferase I or II. Three individuals from two families were found that exhibited similar phenotypes. The index case subjects were two brothers, individuals 1 and 2, who presented with osteoporosis, cataracts, sensorineural hearing loss, and mild learning defects. Whole exome sequence analyses showed that both individuals had a homozygous c.692dup mutation (GenBank: <ext-link ext-link-type="uri" xlink:href="ncbi-n:NM_022167.3" id="intref0010">NM_022167.3</ext-link>
) in the xylosyltransferase II locus (<italic>XYLT2</italic>
) (MIM: <ext-link ext-link-type="omim" xlink:href="608125" id="intref0015">608125</ext-link>
), causing reduced <italic>XYLT2</italic>
mRNA and low circulating xylosyltransferase (XylT) activity. In an unrelated boy (individual 3) from the second family, we noted low serum XylT activity. Sanger sequencing of <italic>XYLT2</italic>
in this individual revealed a c.520del mutation in exon 2 that resulted in a frameshift and premature stop codon (p.Ala174Profs<sup>∗</sup>
35). Fibroblasts from individuals 1 and 2 showed a range of defects including reduced XylT activity, GAG incorporation of <sup>35</sup>
SO<sub>4</sub>
, and heparan sulfate proteoglycan assembly. These studies demonstrate that human XylT2 deficiency results in vertebral compression fractures, sensorineural hearing loss, eye defects, and heart defects, a phenotype that is similar to the autosomal-recessive disorder spondylo-ocular syndrome of unknown cause. This phenotype is different from what has been reported in individuals with other linker enzyme deficiencies. These studies illustrate that the cells of the lens, retina, heart muscle, inner ear, and bone are dependent on XylT2 for proteoglycan assembly in humans.</p>
</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Main/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001D09 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Merge/biblio.hfd -nk 001D09 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= LymphedemaV1 |flux= Main |étape= Merge |type= RBID |clé= PMC:4457947 |texte= Homozygosity for Frameshift Mutations in XYLT2 Result in a Spondylo-Ocular Syndrome with Bone Fragility, Cataracts, and Hearing Defects }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Merge/RBID.i -Sk "pubmed:26027496" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Merge/biblio.hfd \ | NlmPubMed2Wicri -a LymphedemaV1
![]() | This area was generated with Dilib version V0.6.31. | ![]() |