Hereditary Syndromes With Signs of Premature Aging

Lessel, Davor; Kubisch, Christian

doi:10.3238/arztebl.2019.0489

Cited by 20 publications

(32 citation statements)

References 35 publications

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“…S1 and S2). Thus, both prematurely developed a combination of symptoms commonly observed in the elderly, i.e., bilateral cataracts, progressive muscular atrophy and early onset cardiomyopathy, similar to the findings in diverse segmental progeroid syndromes (Lessel and Kubisch 2019;Martin 1978Martin , 2005.…”

Section: Case Reportssupporting

confidence: 66%

Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies

et al. 2020

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Biallelic variants in TOR1AIP1, encoding the integral nuclear membrane protein LAP1 (lamina-associated polypeptide 1) with two functional isoforms LAP1B and LAP1C, have initially been linked to muscular dystrophies with variable cardiac and neurological impairment. Furthermore, a recurrent homozygous nonsense alteration, resulting in loss of both LAP1 isoforms, was identified in seven likely related individuals affected by multisystem anomalies with progeroid-like appearance and lethality within the 1st decade of life. Here, we have identified compound heterozygosity in TOR1AIP1 affecting both LAP1 isoforms in two unrelated individuals affected by congenital bilateral hearing loss, ventricular septal defect, bilateral cataracts, mild to moderate developmental delay, microcephaly, mandibular hypoplasia, short stature, progressive muscular atrophy, joint contractures and severe chronic heart failure, with much longer survival. Cellular characterization of primary fibroblasts of one affected individual revealed absence of both LAP1B and LAP1C, constitutively low lamin A/C levels, aberrant nuclear morphology including nuclear cytoplasmic channels, and premature senescence, comparable to findings in other progeroid forms of nuclear envelopathies. We additionally observed an abnormal activation of the extracellular signal-regulated kinase 1/2 (ERK 1/2). Ectopic expression of wild-type TOR1AIP1 mitigated these cellular phenotypes, providing further evidence for the causal role of identified genetic variants. Altogether, we thus further expand the TOR1AIP1associated phenotype by identifying individuals with biallelic loss-of-function variants who survived beyond the 1st decade of life and reveal novel molecular consequences underlying the TOR1AIP1-associated disorders.

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Section: Case Reportssupporting

confidence: 66%

Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies

et al. 2020

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“…In addition to a similar facial appearance amongst many of the patients, other features contributed to an upper-body gestalt in several, i.e., short neck with sloping shoulders, pectus carinatum and relative macrocephaly ( Figure 3B). Finally, amongst the few adult patients in our cohort (seven over 18 years), clinical signs of premature ageing 22 were noted -two women (20 years and 44 years) had progressive hair loss, the latter also had premature atherosclerosis, and a 26 year old male had premature osteoporosis and hair loss.…”

Section: Phenotype Associated With Traf7 Variantsmentioning

confidence: 72%

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

Castilla‐Vallmanya

Selmer

Dimartino

et al. 2020

Genetics in Medicine

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Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma and other cancers, while germline variants have recently been identified in seven patients with a syndrome associating cardiac, facial and digital anomalies with developmental delay. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants through identification and description of 45 new patients, and to determine the effects of the variants at a molecular level through transcriptomic analysis of patient fibroblasts.Methods We performed exome, targeted capture and Sanger sequencing in a series of patients with undiagnosed developmental disorders. Phenotypic and mutational comparisons Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation We hope you will consider our manuscript for publication in Genetics in Medicine and we look forward to hearing your response.

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“…Progeria is the one of premature aging diseases in which the patients usually appear normal at birth. The clinical manifestations are expressed within the first year of life, as in our case [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

A 13-Year-Old Boy from Thailand with Hutchinson-Gilford Progeria Syndrome with Coronary Artery and Aortic Calcification and Non-ST-Segment Elevation Myocardial Infarction (NSTEMI)

et al. 2021

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Hereditary Syndromes With Signs of Premature Aging

Cited by 20 publications

References 35 publications

Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies

Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

A 13-Year-Old Boy from Thailand with Hutchinson-Gilford Progeria Syndrome with Coronary Artery and Aortic Calcification and Non-ST-Segment Elevation Myocardial Infarction (NSTEMI)

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