Wiskott-Aldrich Syndrome in a Girl Caused by Heterozygous WASP Mutation and Extremely Skewed X-Chromosome Inactivation: A Novel Association with Maternal Uniparental Isodisomy 6
Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema and immune deficiency, caused primarily by mutations in the WASP (Wiskott-Aldrich syndrome protein) gene. Female carriers are usually asymptomatic because of the preferential activation of the normal...
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| Veröffentlicht in: | Neonatology (Basel, Switzerland) Switzerland), 2015-01, Vol.107 (3), p.185-190 |
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| creator | Takimoto, Tomohito Takada, Hidetoshi Ishimura, Masataka Kirino, Makiko Hata, Kenichiro Ohara, Osamu Morio, Tomohiro Hara, Toshiro |
| description | Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema and immune deficiency, caused primarily by mutations in the WASP (Wiskott-Aldrich syndrome protein) gene. Female carriers are usually asymptomatic because of the preferential activation of the normal, nonmutated X-chromosome in their hematopoietic cells. We report our observations of a female child with WAS, who displayed symptoms of congenital thrombocytopenia. DNA sequencing analysis of the WASP gene revealed a heterozygous nonsense mutation in exon 10. The expressions of WASP and normal WASP mRNA were defective. We found preferential inactivation of the X-chromosome on which wild-type WASP was located. Single-nucleotide polymorphism microarray testing and the analysis of the polymorphic variable number of tandem repeat regions revealed maternal uniparental isodisomy of chromosome 6 (UPD6). Our results underscore the importance of WASP evaluation in females with congenital thrombocytopenia and suggest that UPD6 might be related to the pathophysiology of nonrandom X-chromosome inactivation. |
| doi_str_mv | 10.1159/000370059 |
| format | Article |
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Female carriers are usually asymptomatic because of the preferential activation of the normal, nonmutated X-chromosome in their hematopoietic cells. We report our observations of a female child with WAS, who displayed symptoms of congenital thrombocytopenia. DNA sequencing analysis of the WASP gene revealed a heterozygous nonsense mutation in exon 10. The expressions of WASP and normal WASP mRNA were defective. We found preferential inactivation of the X-chromosome on which wild-type WASP was located. Single-nucleotide polymorphism microarray testing and the analysis of the polymorphic variable number of tandem repeat regions revealed maternal uniparental isodisomy of chromosome 6 (UPD6). Our results underscore the importance of WASP evaluation in females with congenital thrombocytopenia and suggest that UPD6 might be related to the pathophysiology of nonrandom X-chromosome inactivation.</description><identifier>ISSN: 1661-7800</identifier><identifier>EISSN: 1661-7819</identifier><identifier>DOI: 10.1159/000370059</identifier><identifier>PMID: 25633059</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Case studies ; Chromosomes, Human, X - genetics ; Codon, Nonsense ; Diagnosis ; DNA Mutational Analysis ; Exons ; Female ; Gene mutation ; Genetic aspects ; Genotype ; Heterozygote ; Humans ; Infant ; Novel Insights from Clinical Practice ; Pediatric research ; Sequence Deletion ; Thrombocytopenia ; Uniparental Disomy - genetics ; Wiskott-Aldrich syndrome ; Wiskott-Aldrich Syndrome - genetics ; Wiskott-Aldrich Syndrome Protein - genetics</subject><ispartof>Neonatology (Basel, Switzerland), 2015-01, Vol.107 (3), p.185-190</ispartof><rights>2015 S. Karger AG, Basel</rights><rights>2015 S. Karger AG, Basel.</rights><rights>COPYRIGHT 2015 S. Karger AG</rights><rights>Copyright S. 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Our results underscore the importance of WASP evaluation in females with congenital thrombocytopenia and suggest that UPD6 might be related to the pathophysiology of nonrandom X-chromosome inactivation.</description><subject>Case studies</subject><subject>Chromosomes, Human, X - genetics</subject><subject>Codon, Nonsense</subject><subject>Diagnosis</subject><subject>DNA Mutational Analysis</subject><subject>Exons</subject><subject>Female</subject><subject>Gene mutation</subject><subject>Genetic aspects</subject><subject>Genotype</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Infant</subject><subject>Novel Insights from Clinical Practice</subject><subject>Pediatric research</subject><subject>Sequence Deletion</subject><subject>Thrombocytopenia</subject><subject>Uniparental Disomy - genetics</subject><subject>Wiskott-Aldrich syndrome</subject><subject>Wiskott-Aldrich Syndrome - genetics</subject><subject>Wiskott-Aldrich Syndrome Protein - genetics</subject><issn>1661-7800</issn><issn>1661-7819</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpd0ctu1DAUBuAIgWgpLNgjZAkJwSJgx3Yu3UWjXkZqAWmKyi5y4pOJO0482E7b8Fa8IR4yzIKVz-I7v3X0R9Frgj8RwovPGGOaYcyLJ9ExSVMSZzkpnh5mjI-iF87dBcF5mjyPjhKeUhr8cfT7VrmN8T4utbSq6dBqGqQ1PSA1IIEulNVoIUYHEtUTugQP1vya1mZ06LZcfUPXoxdemWAHic4evYUe9IRWG3gIKz_iRRfCjNsFLgfReHX_l5-iEn0x96BR6Zxp1JzxoHyHrkX4YxAafR_UVlgYfJiXzkgVUiaUvoyetUI7eLV_T6Kb87ObxWV89fViuSiv4oam3McCJ6KoKW0pZ7QoCCVYMJpnDasB521DcpkAgCSykAzamqVU8gYXaSaIyAQ9iT7MsVtrfo7gfNUr14DWYoBwfUVSnjDGcI4DffcfvTPj7oSgMspyxnjOg3o_q7XQUHUgtO-c0ePucleVKc1oKJGxAD_OsLHGOQtttbWqF3aqCK52fVeHvoN9u_96rHuQB_mv4ADezGAj7BrsAez3_wBR3q8N</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Takimoto, Tomohito</creator><creator>Takada, Hidetoshi</creator><creator>Ishimura, Masataka</creator><creator>Kirino, Makiko</creator><creator>Hata, Kenichiro</creator><creator>Ohara, Osamu</creator><creator>Morio, Tomohiro</creator><creator>Hara, Toshiro</creator><general>S. 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Academic</collection><jtitle>Neonatology (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takimoto, Tomohito</au><au>Takada, Hidetoshi</au><au>Ishimura, Masataka</au><au>Kirino, Makiko</au><au>Hata, Kenichiro</au><au>Ohara, Osamu</au><au>Morio, Tomohiro</au><au>Hara, Toshiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wiskott-Aldrich Syndrome in a Girl Caused by Heterozygous WASP Mutation and Extremely Skewed X-Chromosome Inactivation: A Novel Association with Maternal Uniparental Isodisomy 6</atitle><jtitle>Neonatology (Basel, Switzerland)</jtitle><addtitle>Neonatology</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>107</volume><issue>3</issue><spage>185</spage><epage>190</epage><pages>185-190</pages><issn>1661-7800</issn><eissn>1661-7819</eissn><abstract>Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema and immune deficiency, caused primarily by mutations in the WASP (Wiskott-Aldrich syndrome protein) gene. Female carriers are usually asymptomatic because of the preferential activation of the normal, nonmutated X-chromosome in their hematopoietic cells. We report our observations of a female child with WAS, who displayed symptoms of congenital thrombocytopenia. DNA sequencing analysis of the WASP gene revealed a heterozygous nonsense mutation in exon 10. The expressions of WASP and normal WASP mRNA were defective. We found preferential inactivation of the X-chromosome on which wild-type WASP was located. Single-nucleotide polymorphism microarray testing and the analysis of the polymorphic variable number of tandem repeat regions revealed maternal uniparental isodisomy of chromosome 6 (UPD6). Our results underscore the importance of WASP evaluation in females with congenital thrombocytopenia and suggest that UPD6 might be related to the pathophysiology of nonrandom X-chromosome inactivation.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>25633059</pmid><doi>10.1159/000370059</doi><tpages>6</tpages></addata></record> |
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| ispartof | Neonatology (Basel, Switzerland), 2015-01, Vol.107 (3), p.185-190 |
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| source | Karger Journals; MEDLINE; Alma/SFX Local Collection |
| subjects | Case studies Chromosomes, Human, X - genetics Codon, Nonsense Diagnosis DNA Mutational Analysis Exons Female Gene mutation Genetic aspects Genotype Heterozygote Humans Infant Novel Insights from Clinical Practice Pediatric research Sequence Deletion Thrombocytopenia Uniparental Disomy - genetics Wiskott-Aldrich syndrome Wiskott-Aldrich Syndrome - genetics Wiskott-Aldrich Syndrome Protein - genetics |
| title | Wiskott-Aldrich Syndrome in a Girl Caused by Heterozygous WASP Mutation and Extremely Skewed X-Chromosome Inactivation: A Novel Association with Maternal Uniparental Isodisomy 6 |
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