作者：Katherine Kahn, DVM
出處：WebMD醫學新聞
October 14, 2008(麻州波士頓)—一篇新研究結論指出，一種用於自閉症的多基因風險評估檢測，有助於對那些已有家人發生自閉症的小孩，預測其兄弟姊妹發生此異常的風險；Jorg Hager博士和Geraldine Dawson博士，在美國小兒醫學會2008研討會和展示中聯合發表他們的研究發現。Hager博士是研發此一檢測方式的法國公司、IntegraGen的科學主任，Dawson博士是Autism Speaks的科學主任，也擔任IntegraGen的顧問。
使用自閉症基因資源互換的226個家庭的資料，研究者對那些至少有兩個小孩且其中至少有一人罹患自閉症的家庭進行PITX1、ATP2B2、SLC25A12與EN2這些基因的單核苷酸多態性(SNPs)的基因圖排列；兄弟姊妹間沒有自閉症者作為對照組。
計算這四個基因有單一SNP風險對偶基因的頻率，以及風險對偶基因數量增加的勝算比；Hager博士向聽眾表示，風險對偶基因增加時，自閉症風險增加；每個風險對偶基因平均增加1.35 (90% CI, 1.14 – 1.59; P = .002)；不過，如果小孩有全部八種風險對偶基因，勝算比為5.94倍(90% CI, 2.16 – 16.32)。
Hager博士表示，我們希望導入風險閾值，因此我們將這些至少有七個風險對偶基因的高風險小孩分類；當你降低閾值到至少七個風險對偶基因，發生自閉症的機會增加兩倍；這個檢測的專一性為92%，敏感性為16%。
Dawson博士闡述這個風險評估檢測的一些潛在利益；醫師可用這個工具來評估有自閉症兄姐的嬰兒是否有較高的自閉症風險；也可以在出現症狀前使用這個檢測，對這些小孩可能發生的問題能有較大的警覺和監測，該檢測也可以在發現徵兆時使用。
Dawson博士也指出，該檢測有助於早期介入；她向聽眾表示，早期介入可影響結果。已經有早期介入研究指出，早期介入對二至四歲的小孩有明顯影響。
她也強調，這個檢測不是自閉症診斷工具，但可以配合現有的臨床工具來評估小孩有此異常的風險；我們現在邁入一個新紀元，未來也無可避免的有重要的倫理議題。
Alex Kemper醫師向Medscape Pediatrics提出對此研究的看法；令人擔心的是，這個檢測的敏感度低很令人失望 ，但是專一性更重要。這個檢測的專一性為92%，這表示，沒有自閉症的小孩被檢測為陽性的機會有8%。這可能會毀了一個家庭，特別是Dawson博士建議檢測陽性者要增加早期介入與監測。考慮這些檢測的缺點是相當重要的，我們從其他嚴重小兒狀況的研究知道，即使後來發現是偽陽性，家人也會繼續擔心。
Kemper醫師是該場研討會的聽眾之一，是Duke Pediatrics的一名一般小兒科醫師。
IntegraGen贊助此研究。
美國小兒醫學會2008研討會和展示：摘要578。發表於2008年10月12日。
Genetic Test May Help Assess Autism Risk in Siblings of Affected Children
By Katherine Kahn, DVM
Medscape Medical News
October 14, 2008 (Boston, Massachusetts) — A multigene risk assessment test for autism in families that already have an affected first child may help to predict the risk of developing the disorder in siblings, a new study concludes.
Jorg Hager, PhD, and Geraldine Dawson, PhD, jointly presented the findings of their research and its implications here at the American Academy of Pediatrics 2008 National Conference and Exhibition. Dr. Hager is the chief scientific officer of IntegraGen SA, the company that developed the test. Dr. Dawson is the chief scientific officer of Autism Speaks and serves on the advisory board of IntegraGen SA.
Using data on 226 families from the Autism Genetic Resource Exchange, researchers genotyped single nucleotide polymorphisms (SNPs) in the PITX1, ATP2B2, SLC25A12, and EN2 genes in families that had at least 2 children and at least 1 child with autism. Siblings unaffected by autism served as a control group.
The frequency of single SNP risk alleles in the 4 genes and the odds ratios for increasing numbers of risk alleles were calculated. "The risk of autism increases with increasing numbers of risk alleles," Dr. Hager told session attendees. The average increase per risk allele was 1.35 (90% confidence interval [CI], 1.14 – 1.59; P = .002); however, if a child carried the maximum number of 8 risk alleles, the odds ratio was 5.94 (90% CI, 2.16 – 16.32).
"We wanted to introduce a risk threshold, so we classified those children as high risk who have at least 7 risk alleles," Dr. Hager said. "When you reduce the threshold to at least 7 risk alleles then the chance of being autistic increases by 2." The specificity of the test was determined to be 92%, while the sensitivity was 16%.
Dr. Dawson elaborated on some of the potential benefits of the risk assessment test. "This is a tool that a physician could use to assess whether an infant [with an autistic sibling] might be at higher risk for autism. This could be used before symptoms emerge so that greater vigilance and monitoring can occur for that infant, or the test could be used when we start to see the emerging red flags," she said.
Dr. Dawson also pointed out that the test could help lead to earlier intervention. "Early intervention does affect outcome," she told session attendees. "There have been studies of early intensive intervention for children 2 to 4 years of age that shows intervention can have a significant impact on outcome."
She also stressed that this test was not diagnostic for autism, but it could complement existing clinical tools in evaluating children at risk for the disorder. "We are moving into a new era now," she said. "There are significant ethical issues that come with moving in this direction that are inevitable."
Alex Kemper, MD, MPH, commented to Medscape Pediatrics about the study. "Although on first blush the sensitivity of the test is disappointingly low, the specificity may have more important implications," he said. "The fact that the specificity for this test is 92% means there is an 8% chance that if a child didn't have autism, they would testpositive for it. That could be devastating for a family, especially in light of Dr. Dawson's comments that a positive test could allow for increased monitoring and early intervention.
"It's important to consider the potential downside to these types of tests," Dr. Kemper continued. "We know from studying other serious pediatric conditions that even after a false-positive is uncovered as false, families continue to worry." Dr. Kemper, an attendee at the conference, is a general pediatrician at Duke Pediatrics, in Durham, North Carolina.
The study was funded by IntegraGen SA, Evry, France.
American Academy of Pediatrics 2008 National Conference and Exhibition: Abstract 578. Presented October 12, 2008.
[ 本帖最後由 goodcat1111 於 2008-10-22 21:34 編輯 ] |
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