Familial co-occurrence of congenital heart defects follows distinct patterns.
Familial co-occurrence of congenital heart defects follows distinct patterns.
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DOI：
10.1093/eurheartj/ehx314
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发表时间：
2018-03-21
影响因子：
39.3
通讯作者：
Larsen LA
中科院分区：
文献类型：
--
作者：
Ellesøe SG;Workman CT;Bouvagnet P;Loffredo CA;McBride KL;Hinton RB;van Engelen K;Gertsen EC;Mulder BJM;Postma AV;Anderson RH;Hjortdal VE;Brunak S;Larsen LA
先天性心脏病(CHD)影响了几乎1%的活着出生的儿童，而且患有CHD的成年人数量正在增加。在以前发生过CHD的家庭中，复发风险的估计和复发畸形的类型对于咨询和临床决策很重要，但对家庭中的复发模式了解很少。我们的目的是通过调查1163个有已知畸形的家庭中CHD的共生情况来确定复发模式，包括3080名临床确诊的个体。我们计算了41种特定类型畸形的符合率和不符合率，观察到符合率和不符合率的高度可变性。通过计算在受影响的家庭成员之间观察到的1640对不协调病变中的每一对的优势比，我们能够识别出178对畸形，它们在家庭中共同发生的频率明显高于或低于预期。数据显示，不同组的心脏畸形在家族中共同发生，这表明受到潜在发育机制的影响。对人类和小鼠易感基因的分析表明，它们分别在19%和20%的共生不协调畸形中共享，但很少同时发生的畸形中没有一对共享，这表明在家族中有相当大比例的共生病变是由重叠的易感基因引起的。家族性CHD遵循特定的复发模式，表明受到基因调控的发育机制的强烈影响。家族中共同发生的畸形是由共同的易感基因引起的。
Congenital heart defects (CHD) affect almost 1% of all live born children and the number of adults with CHD is increasing. In families where CHD has occurred previously, estimates of recurrence risk, and the type of recurring malformation are important for counselling and clinical decision-making, but the recurrence patterns in families are poorly understood. We aimed to determine recurrence patterns, by investigating the co-occurrences of CHD in 1163 families with known malformations, comprising 3080 individuals with clinically confirmed diagnosis. We calculated rates of concordance and discordance for 41 specific types of malformations, observing a high variability in the rates of concordance and discordance. By calculating odds ratios for each of 1640 pairs of discordant lesions observed between affected family members, we were able to identify 178 pairs of malformations that co-occurred significantly more or less often than expected in families. The data show that distinct groups of cardiac malformations co-occur in families, suggesting influence from underlying developmental mechanisms. Analysis of human and mouse susceptibility genes showed that they were shared in 19% and 20% of pairs of co-occurring discordant malformations, respectively, but none of malformations that rarely co-occur, suggesting that a significant proportion of co-occurring lesions in families is caused by overlapping susceptibility genes. Familial CHD follow specific patterns of recurrence, suggesting a strong influence from genetically regulated developmental mechanisms. Co-occurrence of malformations in families is caused by shared susceptibility genes.
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DOI：
10.1016/s0735-1097(03)00853-2
发表时间：
2003-09-03
影响因子：
24
作者：
Gill, HK;Splitt, M;Simpson, JM
通讯作者：
Simpson, JM
影响因子：
5
作者：
FERENCZ, C;RUBIN, JD;DOWNING, JW
通讯作者：
DOWNING, JW
影响因子：
--
作者：
Chin-Yee, Nicolas J.;Costain, Gregory;Bassett, Anne S.
通讯作者：
Bassett, Anne S.
影响因子：
8
作者：
Andersen, Troels Askhoj;Troelsen, Karin de Linde Lind;Larsen, Lars Allan
通讯作者：
Larsen, Lars Allan
影响因子：
64.8
作者：
Garg, V;Muth, AN;Srivastava, D
通讯作者：
Srivastava, D