Large deletion in PIGL: a common mutational mechanism in CHIME syndrome?
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Genetics and Molecular Biology |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572018000100085 |
Resumo: | Abstract CHIME syndrome is an extremely rare autosomal recessive multisystemic disorder caused by mutations in PIGL. PIGL is an endoplasmic reticulum localized enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which plays a role in the anchorage of cell-surface proteins including receptors, enzymes, and adhesion molecules. Germline mutations in other members of GPI and Post GPI Attachment to Proteins (PGAP) family genes have been described and constitute a group of diseases within the congenital disorders of glycosylation. Patients in this group often present alkaline phosphatase serum levels abnormalities and neurological symptoms. We report a CHIME syndrome patient who harbors a missense mutation c.500T > C (p.Leu167Pro) and a large deletion involving the 5’ untranslated region and part of exon 1 of PIGL. In CHIME syndrome, a recurrent missense mutation c.500T > C (p.Leu167Pro) is found in the majority of patients, associated with a null mutation in the other allele, including an overrepresentation of large deletions. The latter are not detected by the standard analysis in sequencing techniques, including next-generation sequencing. Thus, in individuals with a clinical diagnosis of CHIME syndrome in which only one mutation is found, an active search for a large deletion should be sought. |
id |
SBG-1_57c91d668320034085b9b2a550384634 |
---|---|
oai_identifier_str |
oai:scielo:S1415-47572018000100085 |
network_acronym_str |
SBG-1 |
network_name_str |
Genetics and Molecular Biology |
repository_id_str |
|
spelling |
Large deletion in PIGL: a common mutational mechanism in CHIME syndrome?PIGLCHIME syndromeGPI biosynthesislarge deletionAbstract CHIME syndrome is an extremely rare autosomal recessive multisystemic disorder caused by mutations in PIGL. PIGL is an endoplasmic reticulum localized enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which plays a role in the anchorage of cell-surface proteins including receptors, enzymes, and adhesion molecules. Germline mutations in other members of GPI and Post GPI Attachment to Proteins (PGAP) family genes have been described and constitute a group of diseases within the congenital disorders of glycosylation. Patients in this group often present alkaline phosphatase serum levels abnormalities and neurological symptoms. We report a CHIME syndrome patient who harbors a missense mutation c.500T > C (p.Leu167Pro) and a large deletion involving the 5’ untranslated region and part of exon 1 of PIGL. In CHIME syndrome, a recurrent missense mutation c.500T > C (p.Leu167Pro) is found in the majority of patients, associated with a null mutation in the other allele, including an overrepresentation of large deletions. The latter are not detected by the standard analysis in sequencing techniques, including next-generation sequencing. Thus, in individuals with a clinical diagnosis of CHIME syndrome in which only one mutation is found, an active search for a large deletion should be sought.Sociedade Brasileira de Genética2018-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572018000100085Genetics and Molecular Biology v.41 n.1 2018reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/1678-4685-gmb-2017-0172info:eu-repo/semantics/openAccessCeroni,José RMYamamoto,Guilherme LHonjo,Rachel SKim,Chong APassos-Bueno,Maria RBertola,Débora Reng2018-04-09T00:00:00Zoai:scielo:S1415-47572018000100085Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2018-04-09T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false |
dc.title.none.fl_str_mv |
Large deletion in PIGL: a common mutational mechanism in CHIME syndrome? |
title |
Large deletion in PIGL: a common mutational mechanism in CHIME syndrome? |
spellingShingle |
Large deletion in PIGL: a common mutational mechanism in CHIME syndrome? Ceroni,José RM PIGL CHIME syndrome GPI biosynthesis large deletion |
title_short |
Large deletion in PIGL: a common mutational mechanism in CHIME syndrome? |
title_full |
Large deletion in PIGL: a common mutational mechanism in CHIME syndrome? |
title_fullStr |
Large deletion in PIGL: a common mutational mechanism in CHIME syndrome? |
title_full_unstemmed |
Large deletion in PIGL: a common mutational mechanism in CHIME syndrome? |
title_sort |
Large deletion in PIGL: a common mutational mechanism in CHIME syndrome? |
author |
Ceroni,José RM |
author_facet |
Ceroni,José RM Yamamoto,Guilherme L Honjo,Rachel S Kim,Chong A Passos-Bueno,Maria R Bertola,Débora R |
author_role |
author |
author2 |
Yamamoto,Guilherme L Honjo,Rachel S Kim,Chong A Passos-Bueno,Maria R Bertola,Débora R |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Ceroni,José RM Yamamoto,Guilherme L Honjo,Rachel S Kim,Chong A Passos-Bueno,Maria R Bertola,Débora R |
dc.subject.por.fl_str_mv |
PIGL CHIME syndrome GPI biosynthesis large deletion |
topic |
PIGL CHIME syndrome GPI biosynthesis large deletion |
description |
Abstract CHIME syndrome is an extremely rare autosomal recessive multisystemic disorder caused by mutations in PIGL. PIGL is an endoplasmic reticulum localized enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which plays a role in the anchorage of cell-surface proteins including receptors, enzymes, and adhesion molecules. Germline mutations in other members of GPI and Post GPI Attachment to Proteins (PGAP) family genes have been described and constitute a group of diseases within the congenital disorders of glycosylation. Patients in this group often present alkaline phosphatase serum levels abnormalities and neurological symptoms. We report a CHIME syndrome patient who harbors a missense mutation c.500T > C (p.Leu167Pro) and a large deletion involving the 5’ untranslated region and part of exon 1 of PIGL. In CHIME syndrome, a recurrent missense mutation c.500T > C (p.Leu167Pro) is found in the majority of patients, associated with a null mutation in the other allele, including an overrepresentation of large deletions. The latter are not detected by the standard analysis in sequencing techniques, including next-generation sequencing. Thus, in individuals with a clinical diagnosis of CHIME syndrome in which only one mutation is found, an active search for a large deletion should be sought. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-03-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572018000100085 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572018000100085 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1678-4685-gmb-2017-0172 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
dc.source.none.fl_str_mv |
Genetics and Molecular Biology v.41 n.1 2018 reponame:Genetics and Molecular Biology instname:Sociedade Brasileira de Genética (SBG) instacron:SBG |
instname_str |
Sociedade Brasileira de Genética (SBG) |
instacron_str |
SBG |
institution |
SBG |
reponame_str |
Genetics and Molecular Biology |
collection |
Genetics and Molecular Biology |
repository.name.fl_str_mv |
Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG) |
repository.mail.fl_str_mv |
||editor@gmb.org.br |
_version_ |
1752122388784349184 |