{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:10:51Z","timestamp":1773792651855,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,2,5]],"date-time":"2004-02-05T00:00:00Z","timestamp":1075939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have characterized the molecular basis of \u03b2\u2010hexosaminidase A (HEX A) deficiency in a patient ascertained through an ophthalmologic examination that revealed cherry red spots on his retina. The absence of neurological deficit in this child until 3<jats:styled-content>${\\raise0.5ex\\hbox{3}\\kern-0.1em\/\\kern-0.15em\\lower0.25ex\\hbox{4}}$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-1.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content> years of age indicated residual HEX A must be present. Three <jats:italic>HEXA<\/jats:italic> mutations, 10T\u2009&gt;\u2009C (S4P) and 972T\u2009&gt;\u2009A (V324V) on the maternal allele, and 1A\u2009&gt;\u2009T (M1L) on the paternal allele were identified. The effects of the amino acid substitutions on HEX A expressed in COS\u20107 cells were analyzed; as expected, no HEX A activity was associated with the M1L mutation but surprisingly, the S4P mutation resulted in 59% of the HEX A activity expressed by the wild type cDNA. The effect of the S4P change was much less than that of another <jats:italic>HEXA<\/jats:italic> mutation, G269S, associated with an adult onset form of G<jats:sub>M2<\/jats:sub> gangliosidosis. This indicated that the S4P change was not the cause of disease and suggested that one of the mutations on the maternal allele, 10T\u2009&gt;\u2009C or 972T\u2009&gt;\u2009A, had its effect at the mRNA level. This was confirmed by Northern blot analysis that showed only 7% of the normal level of <jats:italic>HEXA<\/jats:italic> mRNA in proband fibroblasts. Analysis of the residual mRNA by RT\/PCR and sequencing revealed normal transcripts from both the maternal and paternal allele, as well as a low abundance aberrant transcript from the maternal allele. Sequencing of this aberrant transcript revealed a new exon 8 donor site created by the 972T\u2009&gt;\u2009A mutation that resulted in a 17 bp deletion and destabilization of the resulting abnormal transcript. The remaining normal mRNA produced from the 972T\u2009&gt;\u2009A allele must account for the delayed onset of clinical symptoms in this child. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.20633","type":"journal-article","created":{"date-parts":[[2004,4,20]],"date-time":"2004-04-20T18:02:24Z","timestamp":1082484144000},"page":"158-166","source":"Crossref","is-referenced-by-count":12,"title":["Severe subacute G<sub>M2<\/sub> gangliosidosis caused by an apparently silent <i>HEXA<\/i> mutation (V324V) that results in aberrant splicing and reduced <i>HEXA<\/i> mRNA"],"prefix":"10.1002","volume":"127A","author":[{"given":"Brandy A.","family":"Wicklow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Ivanovich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margot 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