{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:00:38Z","timestamp":1761102038906},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Krabbe disease is an autosomal recessive lysosomal storage disorder caused by mutations in the <jats:italic>GALC<\/jats:italic> gene. The most common mutation in the Caucasian population is a 30-kb deletion of exons 11 through 17. There are few other reports of intragenic <jats:italic>GALC<\/jats:italic> deletions or duplications, due in part to difficulties detecting them.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and results<\/jats:title>\n            <jats:p>We used gene-targeted array comparative genomic hybridization (CGH) to analyze the <jats:italic>GALC<\/jats:italic> gene in individuals with Krabbe disease in whom sequence analysis with 30-kb deletion analysis identified only one mutation. In our sample of 33 cases, traditional approaches failed to identify two pathogenic mutations in five (15.2%) individuals with confirmed Krabbe disease. The addition of array CGH deletion\/duplication analysis to the genetic testing strategy led to the identification of a second pathogenic mutation in three (9.1%) of these five individuals. In all three cases, the deletion or duplication identified through array CGH was a novel <jats:italic>GALC<\/jats:italic> mutation, including the only reported duplication in the <jats:italic>GALC<\/jats:italic> gene, which would have been missed by traditional testing methodologies. We report these three cases in detail. The second mutation remains unknown in the remaining two individuals (6.1%), despite our full battery of testing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Analysis of the <jats:italic>GALC<\/jats:italic> gene using array CGH deletion\/duplication testing increased the two-mutation detection rate from 84.8% to 93.9% in affected individuals. Better mutation detection rates are important for improving molecular diagnosis of Krabbe disease, as well as for providing prenatal and carrier testing in family members.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1750-1172-7-38","type":"journal-article","created":{"date-parts":[[2012,7,25]],"date-time":"2012-07-25T14:23:34Z","timestamp":1343226214000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Array CGH improves detection of mutations in the GALC gene associated with Krabbe disease"],"prefix":"10.1186","volume":"7","author":[{"given":"Alice K","family":"Tanner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ephrem L H","family":"Chin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia K","family":"Duffner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhuri","family":"Hegde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,6,15]]},"reference":[{"key":"380_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/mgme.2000.2990","volume":"70","author":"DA Wenger","year":"2000","unstructured":"Wenger DA, Rafi MA, Luzi P, Datto J, Costantino-Ceccarini E: Krabbe disease: genetic aspects and progress toward therapy. Mol Genet Metab. 2000, 70: 1-9. 10.1006\/mgme.2000.2990.","journal-title":"Mol Genet Metab"},{"key":"380_CR2","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1073\/pnas.66.2.302","volume":"66","author":"K Suzuki","year":"1970","unstructured":"Suzuki K, Suzuki Y: Globoid Cell Leukodystrophy (Krabbe's Disease): Deficiency of Galactocerebroside beta-Galactosidase. Proc Natl Acad Sci. 1970, 66: 302-309. 10.1073\/pnas.66.2.302.","journal-title":"Proc Natl Acad Sci"},{"key":"380_CR3","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1002\/(SICI)1098-1004(1997)10:4<268::AID-HUMU2>3.0.CO;2-D","volume":"10","author":"DA Wenger","year":"1997","unstructured":"Wenger DA, Rafi MA, Luzi P: Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications. 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Genet Med. 2010, 12: 539-543. 10.1097\/GIM.0b013e3181e85721.","journal-title":"Genet Med"},{"key":"380_CR5","volume-title":"Krabbe disease online NIH gene review","author":"DA Wenger","year":"2011","unstructured":"Wenger DA: Krabbe disease online NIH gene review. 2011, Available at http:\/\/wwwncbinlmnihgov\/books\/NBK1238\/Accessed February 25"},{"key":"380_CR6","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1001\/archneur.60.11.1643","volume":"60","author":"I Korn-Lubetzki","year":"2003","unstructured":"Korn-Lubetzki I, Nevo Y: Infantile Krabbe disease. Arch Neurol. 2003, 60: 1643-1644. 10.1001\/archneur.60.11.1643.","journal-title":"Arch Neurol"},{"key":"380_CR7","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1093\/hmg\/2.11.1841","volume":"2","author":"YQ Chen","year":"1993","unstructured":"Chen YQ, Rafi MA, de Gala G, Wenger DA: Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme deficient in globoid cell leukodystrophy. 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