{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:16:51Z","timestamp":1785536211058,"version":"3.56.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,3,22]],"date-time":"2011-03-22T00:00:00Z","timestamp":1300752000000},"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 B"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We present a family with mild developmental delay and a duplication (6)(p22.2). Array CGH analyses revealed this 0.7\u2009Mb duplication in all three patients, spanning candidate genes <jats:italic>ALDH5A1<\/jats:italic>, <jats:italic>DCDC2<\/jats:italic>, and <jats:italic>KIAA0319<\/jats:italic>. Results were confirmed by MLPA analysis of the dyslexia genes <jats:italic>DCDC2<\/jats:italic> and <jats:italic>KIAA0319<\/jats:italic>. Of interest, <jats:italic>ALDH5A1<\/jats:italic> encodes succinate semialdehyde dehydrogenase (SSADH), an enzyme responsible for \u03b3\u2010amino\u2010butyric acid (GABA) degradation. Inherited deficiency of SSADH results in accumulation of the neuromodulator \u03b3\u2010hydroxybutyrate (GHB), which likely contributes to some aspects of the neurological phenotype of SSADH deficiency (MIM #271980). Based on autosomal\u2010recessive inheritance, we sequenced <jats:italic>ALDH5A1<\/jats:italic> in all patients, which revealed no pathogenic mutations. SSADH enzyme studies in cultured white cells confirmed elevated SSADH activity, consistent with the duplication, whereas concentrations of SSA were slightly elevated in urine, suggesting oxidant stress. We speculate that the duplication (6)(p22.2) and corresponding hyperactive level of SSADH activity may have negative consequences for GABA metabolism and the role of SSADH in other metabolic sequences. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.31180","type":"journal-article","created":{"date-parts":[[2011,3,22]],"date-time":"2011-03-22T16:06:45Z","timestamp":1300810005000},"page":"448-453","source":"Crossref","is-referenced-by-count":5,"title":["Familial 6p22.2 duplication associates with mild developmental delay and increased SSADH activity"],"prefix":"10.1002","volume":"156","author":[{"given":"Linda","family":"Siggberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Mustonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Schuit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajja S.","family":"Salomons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birthe","family":"Roos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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