More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations.
More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations.
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DOI：
10.1016/j.jaad.2018.09.042
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发表时间：
2019-03
影响因子：
13.8
通讯作者：
Milstone LM
中科院分区：
文献类型：
--
作者：
Lilly E;Bunick CG;Maley AM;Zhang S;Spraker MK;Theos AJ;Vivar KL;Seminario-Vidal L;Bennett AE;Sidbury R;Ogawa Y;Akiyama M;Binder B;Hadj-Rabia S;Morotti RA;Glusac EJ;Choate KA;Richard G;Milstone LM
KID综合征的婴儿死亡是公认的，其与特定基因型和病理生理学的关系尚未充分了解。发现致死性KID综合征不良结局的特征。我们收集了4例新病例和9例先前报告的致死性KID综合征基因分型病例。我们对致死突变体GJB 2 p.A88V和GJB 2 p.G45E进行了新的分子建模。婴儿死亡发生在所有GJB 2 p.G45E和p.A88V患者中;这在其他GJB 2突变中并不常见。这两种“致命”突变导致的早期死亡可能是多因素造成的：在生命中，所有人都至少有一次严重感染;大多数人体重增加不佳，呼吸困难严重;许多人有其他解剖异常。GJB 2 p.G45E的结构建模确定对先前预测的盐桥没有影响，以解释GJB 2 p.A88V的异常中心CO2感知。临床回顾是回顾性的。GJB 2 p.G45E和p.A88V是唯一与统一早期致死性相关的KID综合征突变。GJB 2中的这些电生理严重突变揭示了致死性KID综合征中许多器官的异常。所有KID综合征患者可能有眼睛，耳朵和皮肤以外的细微异常。KID综合征出生的早期基因分型将为预后讨论提供信息。
Infant death in KID syndrome is recognized; its association with specific genotypes and pathophysiology is inadequately understood. To discover characteristics that account for poor outcomes in lethal KID syndrome. We collected four new cases and nine previously reported, genotyped cases of lethal KID syndrome. We performed new molecular modeling of the lethal mutants GJB2 p.A88V and GJB2 p.G45E. Infant death occurred in all patients with GJB2 p.G45E and p.A88V; it is unusual with other GJB2 mutations. Early death with those two “lethal” mutations is likely multifactorial: during life all had at least one serious infection; most had poor weight gain and severe respiratory difficulties; many had additional anatomic abnormalities. Structural modeling of GJB2 p.G45E identified no impact on the salt bridge previously predicted to account for abnormal central CO2 sensing of GJB2 p.A88V. Clinical review was retrospective. GJB2 p.G45E and p.A88V are the only KID syndrome mutations associated with uniform early lethality. Those electro-physiologically severe mutations in GJB2 reveal abnormalities in many organs in lethal KID syndrome. All KID syndrome patients may have subtle abnormalities beyond eyes, ears and skin. Early genotyping of KID syndrome births will inform prognostic discussion.
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影响因子：
4.5
作者：
Ogawa Y;Takeichi T;Kono M;Hamajima N;Yamamoto T;Sugiura K;Akiyama M
通讯作者：
Akiyama M
DOI：
10.1085/jgp.201010433
发表时间：
2010-07
期刊：
The Journal of general physiology
影响因子：
--
作者：
Sánchez HA;Mese G;Srinivas M;White TW;Verselis VK
通讯作者：
Verselis VK
影响因子：
7.3
作者：
Lilly E;Sellitto C;Milstone LM;White TW
通讯作者：
White TW
影响因子：
7.7
作者：
Meigh, Louise;Greenhalgh, Sophie A.;Dale, Nicholas
通讯作者：
Dale, Nicholas
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K