15.05.2013 | Mardi J. Sutherland; Shuyun Wang; Malgorzata E. Quinn; Allison Haaning; Stephanie M. Ware, Human Molecular Genetics, 2013

In humans, loss-of-function mutations in ZIC3 cause isolated cardiovascular malformations and X-linked heterotaxy, a disorder with abnormal left–right asymmetry of organs. Zic3 null mice recapitulate the human heterotaxy phenotype but also have early gastrulation defects, axial patterning ...

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15.05.2013 | Amanda C. Leightner; Cynthia J. Hommerding; Ying Peng; Jeffrey L. Salisbury; Vladimir G. Gainullin; Peter G. Czarnec ..., Human Molecular Genetics, 2013

Meckel syndrome (MKS) is a lethal disorder associated with renal cystic disease, encephalocele, ductal plate malformation and polydactyly. MKS is genetically heterogeneous and part of a growing list of syndromes called ciliopathies, disorders resulting from defective cilia. TMEM67 mutation ...

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15.05.2013 | Rajalaxmi Natarajan; Deepti Trivedi-Vyas; Yogesh P. Wairkar, Human Molecular Genetics, 2013

Mutations in the tuberous sclerosis complex (TSC) are associated with various forms of neurodevelopmental disorders, including autism and epilepsy. The heterodimeric TSC complex, consisting of Tsc1 and Tsc2 proteins, regulates the activity of the TOR (target of rapamycin) complex via Rheb, a ...

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01.05.2013 | Han-Yun Hsiao; Yu-Chen Chen; Hui-Mei Chen; Pang-Hsien Tu; Yijuang Chern, Human Molecular Genetics, 2013

Huntington's disease (HD) is an autosomal disease caused by a CAG repeat expansion in the huntingtin (HTT) gene. The resultant mutant HTT protein (mHTT) forms aggregates in various types of cells, including neurons and glial cells and preferentially affects brain function. We found that two ...

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01.05.2013 | Melissa S. Cobb; Ferril F. Rose; Hansjörg Rindt; Jacqueline J. Glascock; Monir Shababi; Madeline R. Miller; Erkan Y. ..., Human Molecular Genetics, 2013

Spinal Muscular Atrophy (SMA) is due to the loss of the survival motor neuron gene 1 (SMN1), resulting in motor neuron (MN) degeneration, muscle atrophy and loss of motor function. While SMN2 encodes a protein identical to SMN1, a single nucleotide difference in exon 7 causes most of the ...

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01.05.2013 | Sophie Monnot; David C. Samuels; Laetitia Hesters; Nelly Frydman; Nadine Gigarel; Philippe Burlet; Violaine Kerbrat; ..., Human Molecular Genetics, 2013

Mitochondrial DNA (mtDNA) content is thought to remain stable over the preimplantation period of human embryogenesis that is, therefore, suggested to be entirely dependent on ooplasm mtDNA capital. We have explored the impact of two disease-causing mutations [m.3243A>G myopathy, ...

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01.05.2013 | Andrew Johnston; Xianying Xing; William R. Swindell; James Kochkodan; MaryBeth Riblett; Rajan P. Nair; Philip E. Stu ..., Human Molecular Genetics, 2013

The IL12B gene encodes the common p40 subunit of IL-12 and IL-23, cytokines with key roles in Th1 and Th17 biology, respectively, and genetic variation in this region significantly influences risk of psoriasis. Here, we demonstrate that a psoriasis-associated risk haplotype at the IL12B ...

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01.05.2013 | Romain Joubert; Alban Vignaud; Mickaël Le; Christelle Moal; Nadia Messaddeq; Anna Buj-Bello, Human Molecular Genetics, 2013

Manipulation of the mouse genome by site-specific mutagenesis has been extensively used to study gene function and model human disorders. Mouse models of myotubular myopathy (XLMTM), a severe congenital muscular disorder due to loss-of-function mutations in the MTM1 gene, have been generated ...

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01.05.2013 | Samuel M. Lee; Di Sha; Anum A. Mohammed; Seneshaw Asress; Jonathan D. Glass; Lih-Shen Chin; Lian Li, Human Molecular Genetics, 2013

Charcot–Marie–Tooth disease type 1C (CMT1C) is a dominantly inherited motor and sensory neuropathy. Despite human genetic evidence linking missense mutations in SIMPLE to CMT1C, the in vivo role of CMT1C-linked SIMPLE mutations remains undetermined. To investigate the molecular mechanism ...

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01.05.2013 | Daniel Dreidax; Sina Gogolin; Christina Schroeder; Daniel Muth; Lena Marie Brueckner; Elisa Maria Hess; Marc Zapatka ..., Human Molecular Genetics, 2013

The TP53 tumor suppressor pathway is abrogated by TP53 mutations in the majority of human cancers. Increased levels of wild-type TP53 in aggressive neuroblastomas appear paradox but are tolerated by tumor cells due to co-activation of the TP53 ubiquitin ligase, MDM2. The role of the MDM2 ...

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