De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing.
De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing.
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DOI：
10.1186/1471-2350-15-49
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发表时间：
2014-05-01
影响因子：
--
通讯作者：
Quintero-Rivera F
中科院分区：
文献类型：
--
作者：
Strom SP;Lozano R;Lee H;Dorrani N;Mann J;O'Lague PF;Mans N;Deignan JL;Vilain E;Nelson SF;Grody WW;Quintero-Rivera F
维德曼-施泰纳综合征 (WSS) 的特点是身材矮小、各种面部和骨骼特征畸形、特征性肘部毛发过多（肘部毛发过多）、轻至中度发育迟缓和智力障碍。 [MIM#：605130]。在这里，我们报告了两名没有血缘关系的儿童，他们在加州大学洛杉矶分校对其父母-先证者三人组进行了临床外显子组测序，结果得到了 WSS 的分子诊断和不典型的临床表现。对于患者 1，9 岁时的临床特征包括发育迟缓、颅面异常和多种轻微异常。患者 2 在 1 岁时出现发育迟缓、小眼症、左手部分 3-4 并趾和颅面异常。患者 1 和患者 2 的 KMT2A 基因中分别鉴定出从头错义 c.4342T>C 变体和从头剪接位点 c.4086+G>A 变体。根据临床和分子发现，两名患者似乎都有 WSS 的新表现。由于这两种情况最初都没有意识到标志性的肘部多毛症，因此在临床评估过程中并未怀疑这种综合征。该报告扩展了与 WSS 相关的临床表型和 KMT2A 变异的表型谱。
Wiedemann-Steiner Syndrome (WSS) is characterized by short stature, a variety of dysmorphic facial and skeletal features, characteristic hypertrichosis cubiti (excessive hair on the elbows), mild-to-moderate developmental delay and intellectual disability. [MIM#: 605130]. Here we report two unrelated children for whom clinical exome sequencing of parent-proband trios was performed at UCLA, resulting in a molecular diagnosis of WSS and atypical clinical presentation. For patient 1, clinical features at 9 years of age included developmental delay, craniofacial abnormalities, and multiple minor anomalies. Patient 2 presented at 1 year of age with developmental delay, microphthalmia, partial 3–4 left hand syndactyly, and craniofacial abnormalities. A de novo missense c.4342T>C variant and a de novo splice site c.4086+G>A variant were identified in the KMT2A gene in patients 1 and 2, respectively. Based on the clinical and molecular findings, both patients appear to have novel presentations of WSS. As the hallmark hypertrichosis cubiti was not initially appreciated in either case, this syndrome was not suspected during the clinical evaluation. This report expands the phenotypic spectrum of the clinical phenotypes and KMT2A variants associated with WSS.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Desmet FO;Hamroun D;Lalande M;Collod-Béroud G;Claustres M;Béroud C
通讯作者：
Béroud C
影响因子：
16
作者：
Milne, TA;Briggs, SD;Hess, JL
通讯作者：
Hess, JL
影响因子：
9.8
作者：
Gibson, William T.;Hood, Rebecca L.;Jones, Steven J. M.
通讯作者：
Jones, Steven J. M.
影响因子：
4
作者：
MACDERMOT, KD;PATTON, MA;WINTER, RM
通讯作者：
WINTER, RM