The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene
Background Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF). Procedure We studied the ons...
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| Veröffentlicht in: | Pediatric blood & cancer 2017-07, Vol.64 (7), p.n/a |
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| creator | Inoue, Hirofumi Terachi, Shin‐ichi Uchiumi, Takeshi Sato, Tetsuji Urata, Michiyo Ishimura, Masataka Koga, Yui Hotta, Taeko Hara, Toshiro Kang, Dongchon Ohga, Shouichi |
| description | Background
Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF).
Procedure
We studied the onset of disease and the genotype of 22 PC‐deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan.
Results
Twenty‐two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of |
| doi_str_mv | 10.1002/pbc.26404 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1861594771</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1861594771</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3544-63a3f67bd626f3480fdbadedc9a7a780964c796cde9d18f2a7922d748c2cdb5d3</originalsourceid><addsrcrecordid>eNpdkctOwzAQRS0EoqWw4AeQJTZsSu3E8WMJFS-pEizK2nLsCXWVOKFJVPXvcR8UidVcac7cGc1F6JqSe0pIMmlye59wRtgJGtKMZeOMUHF61EQN0EXbLiPKSSbP0SCRlFKp6BAt5wvAtvTBW1PiZgUthM50vg7YBIe_INTdpgFcF7FZd-ADnmIHhbcegt3gte8W2NV9XgKu-v1ku6W76Ps3EX3gEp0Vpmzh6lBH6PP5aT59Hc_eX96mD7OxTTPGxjw1acFF7njCi5RJUrjcOHBWGWGEJIozKxS3DpSjskiMUEniBJM2sS7PXDpCd3vfuP67h7bTlW8tlKUJUPetppLTTDEhaERv_6HLul-FeJ2mKv6QKalkpG4OVJ9X4HSz8pVZbfTvFyMw2QNrX8Lm2KdEb-PRMR69i0d_PE53Iv0ByQOCGw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1901749898</pqid></control><display><type>article</type><title>The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene</title><source>Access via Wiley Online Library</source><source>MEDLINE</source><creator>Inoue, Hirofumi ; Terachi, Shin‐ichi ; Uchiumi, Takeshi ; Sato, Tetsuji ; Urata, Michiyo ; Ishimura, Masataka ; Koga, Yui ; Hotta, Taeko ; Hara, Toshiro ; Kang, Dongchon ; Ohga, Shouichi</creator><creatorcontrib>Inoue, Hirofumi ; Terachi, Shin‐ichi ; Uchiumi, Takeshi ; Sato, Tetsuji ; Urata, Michiyo ; Ishimura, Masataka ; Koga, Yui ; Hotta, Taeko ; Hara, Toshiro ; Kang, Dongchon ; Ohga, Shouichi</creatorcontrib><description>Background
Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF).
Procedure
We studied the onset of disease and the genotype of 22 PC‐deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan.
Results
Twenty‐two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19–52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late‐onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset.
Conclusions
The genotype of double‐PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).</description><identifier>ISSN: 1545-5009</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.26404</identifier><identifier>PMID: 28111891</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adolescent ; Age ; C gene ; Child, Preschool ; compound heterozygous mutation ; Female ; Genotype ; Genotype & phenotype ; Hematology ; Hemorrhage ; Humans ; Infant, Newborn ; Japan ; Male ; Middle Aged ; Mutants ; Mutation ; Neonates ; Oncology ; Pc gene ; pediatric stroke ; pediatric thrombophilia ; Pediatrics ; Polymerase Chain Reaction ; Protein C ; Protein C - genetics ; protein C deficiency ; Protein C Deficiency - genetics ; Protein deficiency ; Proteins ; Purpura ; purpura fulminans ; Stroke ; Thromboembolism ; Thrombophilia ; Time measurement ; Young Adult</subject><ispartof>Pediatric blood & cancer, 2017-07, Vol.64 (7), p.n/a</ispartof><rights>2017 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3544-63a3f67bd626f3480fdbadedc9a7a780964c796cde9d18f2a7922d748c2cdb5d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.26404$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.26404$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28111891$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Inoue, Hirofumi</creatorcontrib><creatorcontrib>Terachi, Shin‐ichi</creatorcontrib><creatorcontrib>Uchiumi, Takeshi</creatorcontrib><creatorcontrib>Sato, Tetsuji</creatorcontrib><creatorcontrib>Urata, Michiyo</creatorcontrib><creatorcontrib>Ishimura, Masataka</creatorcontrib><creatorcontrib>Koga, Yui</creatorcontrib><creatorcontrib>Hotta, Taeko</creatorcontrib><creatorcontrib>Hara, Toshiro</creatorcontrib><creatorcontrib>Kang, Dongchon</creatorcontrib><creatorcontrib>Ohga, Shouichi</creatorcontrib><title>The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene</title><title>Pediatric blood & cancer</title><addtitle>Pediatr Blood Cancer</addtitle><description>Background
Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF).
Procedure
We studied the onset of disease and the genotype of 22 PC‐deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan.
Results
Twenty‐two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19–52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late‐onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset.
Conclusions
The genotype of double‐PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).</description><subject>Adolescent</subject><subject>Age</subject><subject>C gene</subject><subject>Child, Preschool</subject><subject>compound heterozygous mutation</subject><subject>Female</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Hematology</subject><subject>Hemorrhage</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Japan</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Neonates</subject><subject>Oncology</subject><subject>Pc gene</subject><subject>pediatric stroke</subject><subject>pediatric thrombophilia</subject><subject>Pediatrics</subject><subject>Polymerase Chain Reaction</subject><subject>Protein C</subject><subject>Protein C - genetics</subject><subject>protein C deficiency</subject><subject>Protein C Deficiency - genetics</subject><subject>Protein deficiency</subject><subject>Proteins</subject><subject>Purpura</subject><subject>purpura fulminans</subject><subject>Stroke</subject><subject>Thromboembolism</subject><subject>Thrombophilia</subject><subject>Time measurement</subject><subject>Young Adult</subject><issn>1545-5009</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctOwzAQRS0EoqWw4AeQJTZsSu3E8WMJFS-pEizK2nLsCXWVOKFJVPXvcR8UidVcac7cGc1F6JqSe0pIMmlye59wRtgJGtKMZeOMUHF61EQN0EXbLiPKSSbP0SCRlFKp6BAt5wvAtvTBW1PiZgUthM50vg7YBIe_INTdpgFcF7FZd-ADnmIHhbcegt3gte8W2NV9XgKu-v1ku6W76Ps3EX3gEp0Vpmzh6lBH6PP5aT59Hc_eX96mD7OxTTPGxjw1acFF7njCi5RJUrjcOHBWGWGEJIozKxS3DpSjskiMUEniBJM2sS7PXDpCd3vfuP67h7bTlW8tlKUJUPetppLTTDEhaERv_6HLul-FeJ2mKv6QKalkpG4OVJ9X4HSz8pVZbfTvFyMw2QNrX8Lm2KdEb-PRMR69i0d_PE53Iv0ByQOCGw</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>Inoue, Hirofumi</creator><creator>Terachi, Shin‐ichi</creator><creator>Uchiumi, Takeshi</creator><creator>Sato, Tetsuji</creator><creator>Urata, Michiyo</creator><creator>Ishimura, Masataka</creator><creator>Koga, Yui</creator><creator>Hotta, Taeko</creator><creator>Hara, Toshiro</creator><creator>Kang, Dongchon</creator><creator>Ohga, Shouichi</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201707</creationdate><title>The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene</title><author>Inoue, Hirofumi ; Terachi, Shin‐ichi ; Uchiumi, Takeshi ; Sato, Tetsuji ; Urata, Michiyo ; Ishimura, Masataka ; Koga, Yui ; Hotta, Taeko ; Hara, Toshiro ; Kang, Dongchon ; Ohga, Shouichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3544-63a3f67bd626f3480fdbadedc9a7a780964c796cde9d18f2a7922d748c2cdb5d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Age</topic><topic>C gene</topic><topic>Child, Preschool</topic><topic>compound heterozygous mutation</topic><topic>Female</topic><topic>Genotype</topic><topic>Genotype & phenotype</topic><topic>Hematology</topic><topic>Hemorrhage</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Japan</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Neonates</topic><topic>Oncology</topic><topic>Pc gene</topic><topic>pediatric stroke</topic><topic>pediatric thrombophilia</topic><topic>Pediatrics</topic><topic>Polymerase Chain Reaction</topic><topic>Protein C</topic><topic>Protein C - genetics</topic><topic>protein C deficiency</topic><topic>Protein C Deficiency - genetics</topic><topic>Protein deficiency</topic><topic>Proteins</topic><topic>Purpura</topic><topic>purpura fulminans</topic><topic>Stroke</topic><topic>Thromboembolism</topic><topic>Thrombophilia</topic><topic>Time measurement</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Inoue, Hirofumi</creatorcontrib><creatorcontrib>Terachi, Shin‐ichi</creatorcontrib><creatorcontrib>Uchiumi, Takeshi</creatorcontrib><creatorcontrib>Sato, Tetsuji</creatorcontrib><creatorcontrib>Urata, Michiyo</creatorcontrib><creatorcontrib>Ishimura, Masataka</creatorcontrib><creatorcontrib>Koga, Yui</creatorcontrib><creatorcontrib>Hotta, Taeko</creatorcontrib><creatorcontrib>Hara, Toshiro</creatorcontrib><creatorcontrib>Kang, Dongchon</creatorcontrib><creatorcontrib>Ohga, Shouichi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inoue, Hirofumi</au><au>Terachi, Shin‐ichi</au><au>Uchiumi, Takeshi</au><au>Sato, Tetsuji</au><au>Urata, Michiyo</au><au>Ishimura, Masataka</au><au>Koga, Yui</au><au>Hotta, Taeko</au><au>Hara, Toshiro</au><au>Kang, Dongchon</au><au>Ohga, Shouichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2017-07</date><risdate>2017</risdate><volume>64</volume><issue>7</issue><epage>n/a</epage><issn>1545-5009</issn><eissn>1545-5017</eissn><abstract>Background
Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF).
Procedure
We studied the onset of disease and the genotype of 22 PC‐deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan.
Results
Twenty‐two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19–52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late‐onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset.
Conclusions
The genotype of double‐PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28111891</pmid><doi>10.1002/pbc.26404</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Age C gene Child, Preschool compound heterozygous mutation Female Genotype Genotype & phenotype Hematology Hemorrhage Humans Infant, Newborn Japan Male Middle Aged Mutants Mutation Neonates Oncology Pc gene pediatric stroke pediatric thrombophilia Pediatrics Polymerase Chain Reaction Protein C Protein C - genetics protein C deficiency Protein C Deficiency - genetics Protein deficiency Proteins Purpura purpura fulminans Stroke Thromboembolism Thrombophilia Time measurement Young Adult |
| title | The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene |
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