Dodhia Sonam, Celis Katrina, Aylward Alana, Cai Yi, Fontana Maria E, Trespalacios Alberto, Hoffman David C, Alfonso Henry Ostos, Eisig Sidney B, Su Gloria H, Chung Wendy K, Haddad Joseph
Department of Otolaryngology-Head and Neck Surgery, Columbia University Medical Center, New York, New York, U.S.A.
John P. Hussman Institute for Genomics, University of Miami, Miami, Florida, U.S.A.
Laryngoscope. 2017 Oct;127(10):E336-E339. doi: 10.1002/lary.26637. Epub 2017 May 23.
OBJECTIVES/HYPOTHESIS: A candidate variant (p.Val496Ala) of the ACSS2 gene (T > C missense, rs59088485 variant at chr20: bp37 33509608) was previously found to consistently segregate with nonsyndromic cleft lip and/or palate (NSCLP) in three Honduran families. Objectives of this study were 1) to investigate the frequency of this ACSS2 variant in Honduran unrelated NSCLP patients and unrelated unaffected controls and 2) to investigate the frequency of this variant in Colombian unrelated affected NSCLP patients and unrelated unaffected controls. STUDY DESIGN: Case-control studies. METHODS: Sanger sequencing of 99 unrelated Honduran NSCLP patients and 215 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. Sanger sequencing of 230 unrelated Colombian NSCLP patients and 146 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. RESULTS: In the Honduran population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 4.0 (P = .03), with a carrier frequency of seven of 99 (7.1%) in unrelated affected and four of 215 (1.9%) in unrelated unaffected individuals. In the Colombian population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 2.6 (P = .04), with a carrier frequency of 23 of 230 (10.0%) in unrelated affected and six of 146 (4.1%) in unrelated unaffected individuals. CONCLUSIONS: These findings support the role of ACSS2 in NSCLP in two independent Hispanic populations from Honduras and Colombia. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E336-E339, 2017.
目的/假设：先前在三个洪都拉斯家庭中发现，ACSS2基因的一个候选变异（p.Val496Ala，20号染色体上的T > C错义突变，rs59088485变异，位置为bp37 33509608）与非综合征性唇裂和/或腭裂（NSCLP）始终相关。本研究的目的是：1）调查该ACSS2变异在洪都拉斯非亲属NSCLP患者和非亲属未受影响对照中的频率；2）调查该变异在哥伦比亚非亲属受影响NSCLP患者和非亲属未受影响对照中的频率。 研究设计：病例对照研究。 方法：对99名非亲属的洪都拉斯NSCLP患者和215名非亲属未受影响对照进行p.Val496Ala ACSS2变异的桑格测序，以确定NSCLP患者和对照中的携带频率。对230名非亲属的哥伦比亚NSCLP患者和146名非亲属未受影响对照进行p.Val496Ala ACSS2变异的桑格测序，以确定NSCLP患者和对照中的携带频率。 结果：在洪都拉斯人群中，p.Val496Ala ACSS2变异携带者患NSCLP的比值比为4.0（P = .03），在非亲属受影响个体中，携带者频率为99人中的7人（7.1%），在非亲属未受影响个体中为215人中的4人（1.9%）。在哥伦比亚人群中，p.Val496Ala ACSS2变异携带者患NSCLP的比值比为2.6（P = .04），在非亲属受影响个体中，携带者频率为230人中的23人（10.0%），在非亲属未受影响个体中为146人中的6人（4.1%）。 结论：这些发现支持了ACSS2在来自洪都拉斯和哥伦比亚两个独立西班牙裔人群的NSCLP中的作用。 证据水平：无 喉镜，127:E336 - E339，2017年。
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