Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome

Bellucco, Fernanda Teixeira da Silva; Nunes, Natalia Neto dos Santos; Colovati, Mileny Esbravatti Stephano; Malinverni, Andréa Cristina de Moraes; Caneloi, Thamy P.; Soares, Maria Raquel; Pérez, Ana B.; Melaragno, Maria Isabel

doi:10.1159/000477920

Cited by 3 publications

(1 citation statement)

References 12 publications

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“…In particular, deletions of PAFAH1B1 , YWHAE , and CRK genes are associated with severe brain malformation, dysmorphic features, and intrauterine growth retardation. Because the sizes of the deletions vary among affected individuals, additional genes in the deleted regions are likely to contribute to the heterogeneity of MDS features [Dobyns et al, 1993;Cardoso et al, 2003;Bruno et al, 2010;Chen et al, 2013;Bellucco et al, 2017].…”

Section: Discussionmentioning

confidence: 99%

Rare Concurrence of Two Congenital Disorders: Miller-Dieker Syndrome and T-Cell Lymphopenia

Chee¹,

Guo

Huang³

et al. 2019

Cytogenet Genome Res

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Miller-Dieker syndrome (MDS; OMIM 247200) is a rare contiguous gene deletion syndrome associated with lissencephaly and characteristic facial dysmorphism. T-cell lymphopenia is an immunodeficiency disorder which can be early detected by newborn blood screening, and all live vaccines should be avoided. We report a 2.32-Mb microdeletion at chromosome 17p13.3p13.2 and T-cell lymphopenia in a 6-month-old male infant with MDS. This is, to our knowledge, the first description of these 2 conditions co-occurring in the same patient.

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Section: Discussionmentioning

confidence: 99%

Rare Concurrence of Two Congenital Disorders: Miller-Dieker Syndrome and T-Cell Lymphopenia

Chee¹,

Guo

Huang³

et al. 2019

Cytogenet Genome Res

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The Emerging Roles ofLIS1 Biomechanics in Cellular and Cortical Homeostasis

Kshirsagarand,

Reiner

2023

Neocortical Neurogenesis in Development and Evolution

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Multi-Omics Approach Reveals Genes and Pathways Affected in Miller-Dieker Syndrome

Mahendran,

Breger,

McCown

et al. 2024

Mol Neurobiol

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Miller-Dieker syndrome (MDS) is a rare neurogenetic disorder resulting from a heterozygous deletion of 26 genes in the MDS locus on human chromosome 17. MDS patients often die in utero and only 10% of those who are born reach 10 years of age. Current treatments mostly prevent complications and control seizures. A detailed understanding of the pathogenesis of MDS through gene expression studies would be useful in developing precise medical approaches toward MDS. To better understand MDS at the molecular level, we performed RNA sequencing on RNA and mass spectrometry on total protein isolated from BJ (non-MDS) cells and GM06097 (MDS) cells, which were derived from a healthy individual and an MDS patient, respectively. Differentially expressed genes (DEGs) at the RNA and protein levels involved genes associated with phenotypic features reported in MDS patients (CACNG4, ADD2, SPTAN1, SHANK2), signaling pathways (GABBR2, CAMK2B, TRAM-1), and nervous system development (CAMK2B, BEX1, ARSA). Functional assays validated enhanced calcium signaling, downregulated protein translation, and cell migration defects in MDS. Interestingly, overexpression of methyltransferase-like protein 16 (METTL16), a protein encoded in the MDS locus, restored defects in protein translation, phosphor states of mTOR (mammalian target of rapamycin) pathway regulators, and cell migration in MDS cells. Although DNA- and RNA-modifying enzymes were among the DEGs and the intracellular SAM/SAH ratio was eightfold lower in MDS cells, global nucleoside modifications remained unchanged. Thus, this study identified specific genes and pathways responsible for the gene expression changes, which could lead to better therapeutics for MDS patients.

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Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome

Cited by 3 publications

References 12 publications

Rare Concurrence of Two Congenital Disorders: Miller-Dieker Syndrome and T-Cell Lymphopenia

Rare Concurrence of Two Congenital Disorders: Miller-Dieker Syndrome and T-Cell Lymphopenia

The Emerging Roles ofLIS1 Biomechanics in Cellular and Cortical Homeostasis

Multi-Omics Approach Reveals Genes and Pathways Affected in Miller-Dieker Syndrome

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