{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T01:41:04Z","timestamp":1776908464454,"version":"3.51.2"},"reference-count":30,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>Episodic ataxia type 2 (EA2) and familial hemiplegic migraine type 1 (FHM1) are autosomal dominant disorders characterised by paroxysmal ataxia and migraine, respectively. Point mutations in <jats:italic>CACNA1A<\/jats:italic>, which encodes the neuronal P\/Q-type calcium channel, have been detected in many cases of EA2 and FHM1. The genetic basis of typical cases without <jats:italic>CACNA1A<\/jats:italic> point mutations is not fully known. Standard DNA sequencing methods may miss large scale genetic rearrangements such as deletions and duplications. The authors investigated whether large scale genetic rearrangements in <jats:italic>CACNA1A<\/jats:italic> can cause EA2 and FHM1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>The authors used multiplex ligation dependent probe amplification (MLPA) to screen for intragenic <jats:italic>CACNA1A<\/jats:italic> rearrangements.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>The authors identified five previously unreported large scale deletions in <jats:italic>CACNA1A<\/jats:italic> in seven families with episodic ataxia and in one case with hemiplegic migraine. One of the deletions (exon 6 of <jats:italic>CACNA1A<\/jats:italic>) segregated with episodic ataxia in a four generation family with eight affected individuals previously mapped to 19p13. In addition, the authors identified the first pathogenic duplication in <jats:italic>CACNA1A<\/jats:italic> in an index case with isolated episodic diplopia without ataxia and in a first degree relative with episodic ataxia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Large scale deletions and duplications can cause <jats:italic>CACNA1A<\/jats:italic> associated channelopathies. Direct DNA sequencing alone is not sufficient as a diagnostic screening test.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2009.067967","type":"journal-article","created":{"date-parts":[[2009,7,8]],"date-time":"2009-07-08T20:13:25Z","timestamp":1247084005000},"page":"786-791","source":"Crossref","is-referenced-by-count":56,"title":["Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic migraine: implications for diagnostic testing"],"prefix":"10.1136","volume":"46","author":[{"given":"R W","family":"Labrum","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Rajakulendran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T D","family":"Graves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L 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