Mandibuloacral dysplasia

2020 ◽  
Author(s):  
Keyword(s):  
Mandibuloacral Dysplasia

scholarly journals Altered chromatin organization and SUN2 localization in mandibuloacral dysplasia are rescued by drug treatment

2012 ◽  
Vol 138 (4) ◽  
pp. 643-651 ◽  
Author(s):  
Daria Camozzi ◽  
Maria Rosaria D’Apice ◽  
Elisa Schena ◽  
Vittoria Cenni ◽  
Marta Columbaro ◽  
...  
Keyword(s):  
Drug Treatment ◽  
Chromatin Organization ◽  
Mandibuloacral Dysplasia

Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy

2005 ◽  
Vol 23 (2) ◽  
pp. 150-158 ◽  
Author(s):  
Ilaria Filesi ◽  
Francesca Gullotta ◽  
Giovanna Lattanzi ◽  
Maria Rosaria D'Apice ◽  
Cristina Capanni ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Protein A ◽  
Nuclear Architecture ◽  
Mendelian Inheritance ◽  
Premature Aging ◽  
Lamin A ◽  
Lamin B ◽  
Lamin B Receptor ◽  
Epigenetic Events ◽  
Mandibuloacral Dysplasia

Autosomal recessive mandibuloacral dysplasia [mandibuloacral dysplasia type A (MADA); Online Mendelian Inheritance in Man (OMIM) no. 248370 ] is caused by a mutation in LMNA encoding lamin A/C. Here we show that this mutation causes accumulation of the lamin A precursor protein, a marked alteration of the nuclear architecture and, hence, chromatin disorganization. Heterochromatin domains are altered or completely lost in MADA nuclei, consistent with the finding that heterochromatin-associated protein HP1β and histone H3 methylated at lysine 9 and their nuclear envelope partner protein lamin B receptor (LBR) are delocalized and solubilized. Both accumulation of lamin A precursor and chromatin defects become more severe in older patients. These results strongly suggest that altered chromatin remodeling is a key event in the cascade of epigenetic events causing MADA and could be related to the premature-aging phenotype.

Elbow deformities in a patient with mandibuloacral dysplasia type A

2010 ◽  
Vol 152A (11) ◽  
pp. 2711-2713 ◽  
Author(s):  
Valeria Guglielmi ◽  
Monica D'Adamo ◽  
Maria Rosaria D'Apice ◽  
Alfonso Bellia ◽  
Davide Lauro ◽  
...  
Keyword(s):  
Type A ◽  
Mandibuloacral Dysplasia

Mandibuloacral dysplasia with type B lipodystrophy in a patient from Chile

2019 ◽  
Vol 179 (6) ◽  
pp. 893-895 ◽  
Author(s):  
Pablo I. Alarcón ◽  
Ignacia Mujica ◽  
Patricia Sanz ◽  
Cristian J. García ◽  
Simone Gilgenkrantz
Keyword(s):  
Type B ◽  
Mandibuloacral Dysplasia

scholarly journals Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sahar Elouej ◽  
Karim Harhouri ◽  
Morgane Le Mao ◽  
Genevieve Baujat ◽  
Sheela Nampoothiri ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Premature Aging ◽  
Arterial Calcification ◽  
Nuclear Morphology ◽  
C Elegans ◽  
Primary Fibroblasts ◽  
Morphological Defects ◽  
Induced Apoptosis ◽  
And Function ◽  
Mandibuloacral Dysplasia

Abstract Mandibuloacral dysplasia syndromes are mainly due to recessive LMNA or ZMPSTE24 mutations, with cardinal nuclear morphological abnormalities and dysfunction. We report five homozygous null mutations in MTX2, encoding Metaxin-2 (MTX2), an outer mitochondrial membrane protein, in patients presenting with a severe laminopathy-like mandibuloacral dysplasia characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis and severe hypertension. Loss of MTX2 in patients’ primary fibroblasts leads to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients’ fibroblasts are resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Interestingly, secondary nuclear morphological defects are observed in both MTX2-mutant fibroblasts and mtx-2-depleted C. elegans. We thus report the identification of a severe premature aging syndrome revealing an unsuspected link between mitochondrial composition and function and nuclear morphology, establishing a pathophysiological link with premature aging laminopathies and likely explaining common clinical features.

scholarly journals A novel autosomal recessive lipodystrophy syndrome due to homozygous LMNA variant

2019 ◽  
Vol 57 (6) ◽  
pp. 422-426 ◽  
Author(s):  
Nivedita Patni ◽  
Sarah Hatab ◽  
Chao Xing ◽  
Zhengyang Zhou ◽  
Claudia Quittner ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Acanthosis Nigricans ◽  
Subcutaneous Fat ◽  
Subsequent Development ◽  
Muscular Hypertrophy ◽  
Lipodystrophy Syndrome ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Upper And Lower Extremities ◽  
Mandibuloacral Dysplasia

BackgroundDespite major advances in understanding the molecular basis of various genetic lipodystrophy syndromes, some rare patients still remain unexplained.CasesWe report a novel autosomal recessive lipodystrophy affecting two sisters aged 17 and 19 years and characterised by early onset intellectual disability, and subsequent development of near-generalised loss of subcutaneous fat with diabetes mellitus, extreme hypertriglyceridemia, hepatic steatosis, short stature, clinodactyly, joint contractures, leiomyoma of uterus and cataracts in childhood. The lipodystrophy was more pronounced in the upper and lower extremities, and there was no associated muscular hypertrophy. Using whole exome sequencing in this consanguineous Hispanic pedigree, we report disease-causing homozygous p.Arg545His LMNA variant in the affected subjects, and confirm the lack of pathogenic variants in other known lipodystrophy genes. The mother and a younger brother were both heterozygous for p.Arg545His LMNA variant and were overweight with acanthosis nigricans without any evidence of lipodystrophy. Our patients are distinct from previously reported autosomal recessive lipodystrophy syndromes and have no overlap with other autosomal recessive laminopathies, including mandibuloacral dysplasia, Emery-Dreifuss muscular dystrophy and Charcot-Marie-Tooth neuropathy.ConclusionOur report of this unusual familial generalised lipodystrophy syndrome adds to the pleiotropy associated with biallelic autosomal recessive LMNA variants.

A severe case of mandibuloacral dysplasia in a girl

1992 ◽  
Vol 43 (5) ◽  
pp. 877-881 ◽  
Author(s):  
Constance Schrander-Stumpel ◽  
Ann Spaepen ◽  
Jean-Pierre Fryns ◽  
Jan Dumon
Keyword(s):  
Severe Case ◽  
Mandibuloacral Dysplasia
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