{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T16:04:21Z","timestamp":1743782661772},"reference-count":19,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,8,3]],"date-time":"2005-08-03T00:00:00Z","timestamp":1123027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>PRKACA<\/jats:italic> and <jats:italic>PRKACB<\/jats:italic> are genes encoding the cAMP\u2010dependent protein kinase A (PKA) catalytic subunits alpha and beta, respectively. PKA is known to be involved in embryonic development, as it downregulates the Hedgehog (Hh) signaling pathway, which is critical to normal pattern formation and morphogenesis. The PKA\u2010deficient mouse model, which has only a single catalytic subunit, provided intriguing evidence demonstrating a relationship between decreased PKA activity and risk for posterior neural tube defects (NTDs) in the thoracic to sacral regions of gene\u2010knockout mice. Unlike most other mutant mouse models of NTDs, the PKA\u2010deficient mice develop spina bifida with 100% penetrance. We hypothesized that sequence variations in human genes encoding the catalytic subunits may alter the PKA activity and similarly increase the risk of spina bifida.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We sequenced the coding regions and the exon\/intron boundaries of <jats:italic>PRKACA<\/jats:italic> and <jats:italic>PRKACB<\/jats:italic>. We also examined 3 common single\u2010nucleotide polymorphisms (SNPs) of these 2 genes by allele discrimination.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Five sequence variants in coding region and 2 intronic sequence variants proximal to exons were detected. None of the 3 SNPs examined in the association study appeared to be associated with substantially increased risk for spina bifida.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Our results did not reveal a strong association between these PKA SNPs and spina bifida risk. Nonetheless, it is important to examine the possible gene\u2010gene interactions between <jats:italic>PRKACA<\/jats:italic> and <jats:italic>PRKACB<\/jats:italic> when evaluating the risk for NTDs, as well as genes encoding regulatory subunits of PKA. In addition, interactions with other genes such as Sonic Hedgehog (<jats:italic>SHH<\/jats:italic>) should also be considered for future investigations. Birth Defects Research (Part A), 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20175","type":"journal-article","created":{"date-parts":[[2005,8,3]],"date-time":"2005-08-03T21:50:35Z","timestamp":1123105835000},"page":"591-596","source":"Crossref","is-referenced-by-count":14,"title":["Genes encoding catalytic subunits of protein kinase a and risk of spina bifida"],"prefix":"10.1002","volume":"73","author":[{"given":"Huiping","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecile","family":"Laurent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary M.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward J.","family":"Lammer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard H.","family":"Finnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,8,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3016.1991.tb00728.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.9.2885"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00294-002-0308-9"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.6.647"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111412200"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.13.3505"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(200005)61:5<347::AID-TERA6>3.0.CO;2-#"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.0202"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.9.1683"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.17.2250"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(89)90061-4"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0392"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90514-2"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90397-6"},{"key":"e_1_2_6_16_1","first-page":"91","article-title":"Quality control of birth defect registry data: a case study","volume":"108","author":"Schulman J","year":"1993","journal-title":"Public Health Rep"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)93446-V"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.16.3.630"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10045"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0209"}],"container-title":["Birth Defects Research Part A: Clinical and Molecular Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdra.20175","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.20175","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T02:15:05Z","timestamp":1697163305000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.20175"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8,3]]},"references-count":19,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2005,9]]}},"alternative-id":["10.1002\/bdra.20175"],"URL":"https:\/\/doi.org\/10.1002\/bdra.20175","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,8,3]]}}}