期刊论文详细信息
BMC Medical Genetics
De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing
Fabiola Quintero-Rivera2  Wayne W Grody4  Stanley F Nelson5  Eric Vilain4  Joshua L Deignan2  Nicole Mans3  Patricia F O’Lague1  John Mann1  Naghmeh Dorrani3  Hane Lee2  Reymundo Lozano3  Samuel P Strom2 
[1]Department of Genetics, Kaiser Permanente, Fresno, CA, USA
[2]Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
[3]Department of Pediatrics, University of California Davis, Sacramento, CA, USA
[4]Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
[5]Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
关键词: Developmental delay;    Intellectual disability;    KMT2A;    Clinical exome sequencing;    Wiedemann-Steiner syndrome;   
Others  :  1091969
DOI  :  10.1186/1471-2350-15-49
 received in 2013-12-16, accepted in 2014-04-10, published in 15
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【 摘 要 】

Background

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.

Case 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.

Conclusions

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.

【 授权许可】

   
2014 Strom et al.; licensee BioMed Central Ltd.

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