Craniofacial Abnormalities in Hutchinson-Gilford Progeria Syndrome

Ullrich, Nicole J.; Silvera, V. Michelle; Campbell, Susan; Gordon, Leslie B.

doi:10.3174/ajnr.a3088

Cited by 25 publications

(22 citation statements)

References 23 publications

(36 reference statements)

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“…Compared with classic HGPS, she experienced hair loss but not the total alopecia pathognomonic of classic HGPS,11 mandibular recession that is less pronounced than classic HGPS12 and milder than expected joint contractures. Proband birth weight and length patterns were similar to classic HGPS 13.…”

Section: Resultsmentioning

confidence: 85%

A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome

et al. 2016

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BackgroundHutchinson-Gilford progeria syndrome (HGPS) is a fatal sporadic autosomal dominant premature ageing disease caused by single base mutations that optimise a cryptic splice site within exon 11 of the LMNA gene. The resultant disease-causing protein, progerin, acts as a dominant negative. Disease severity relies partly on progerin levels.Methods and resultsWe report a novel form of somatic mosaicism, where a child possessed two cell populations with different HGPS disease-producing mutations of the same nucleotide—one producing severe HGPS and one mild HGPS. The proband possessed an intermediate phenotype. The mosaicism was initially discovered when Sanger sequencing showed a c.1968+2T>A mutation in blood DNA and a c.1968+2T>C in DNA from cultured fibroblasts. Deep sequencing of DNA from the proband's blood revealed 4.7% c.1968+2T>C mutation, and 41.3% c.1968+2T>A mutation.ConclusionsWe hypothesise that the germline mutation was c.1968+2T>A, but a rescue event occurred during early development, where the somatic mutation from A to C at 1968+2 provided a selective advantage. This type of mosaicism where a partial phenotypic rescue event results from a second but milder disease-causing mutation in the same nucleotide has not been previously characterised for any disease.

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Section: Resultsmentioning

confidence: 85%

A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome

et al. 2016

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“…All of the HGPS mutant phenotypes appeared to replicate the clinical manifestations of HGPS in humans (Fig. S5F) (Ozonoff and Clemett, 1967 ; Khalifa, 1989 ; Monu et al, 1990 ; Erdem et al, 1994 ; Stehbens et al, 1999 ; Gordon et al, 2005 ; Hennekam, 2006 ; Merideth et al, 2008 ; Rastogi and Chander Mohan, 2008 ; Doubaj et al, 2011 ; Gordon et al, 2011 ; Ullrich et al, 2012 ; Silvera et al, 2013 ; Chu et al, 2015 ; Ullrich and Gordon, 2015 ; Rivera-Torres et al, 2016 ; Prakash et al, 2018 ; Xu and Jin, 2019 ).…”

Section: Resultsmentioning

confidence: 92%

Generation of a Hutchinson–Gilford progeria syndrome monkey model by base editing

et al. 2020

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Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.

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“…The upper and lower maxilla present variations that are difficult to handle and the frequent dental anomalies impose an accurate study of each patient. 5,6 Developmental defects of the enamel, anomalies in teeth number, position or shape, malocclusion, natal teeth or delayed eruption are reported. For these patients the first dental examination should be planned as soon as the first deciduous tooth erupts in order to promote a tailored preventive plan.…”

Section: Discussionmentioning

confidence: 99%

Special-Needs Patients in Pediatric Dentistry: Progeroid Syndrome. A Case of Dental Management and Oral Rehabilitation

et al. 2019

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This report presents a case of an eight-year-old girl affected by a progeroid syndrome of unclear genetic origins. The patient’s dental history included oligodontia, premature deciduous exfoliation and roots abnormalities. She was treated with comprehensive oral rehabilitation using dentures. Oral health instructions were given during the whole treatment and follow-up period. The goal of improving the masticatory function and the esthetic was achieved, allowing the patient to increase her social abilities and self-confidence.

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Craniofacial Abnormalities in Hutchinson-Gilford Progeria Syndrome

Cited by 25 publications

References 23 publications

A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome

A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome

Generation of a Hutchinson–Gilford progeria syndrome monkey model by base editing

Special-Needs Patients in Pediatric Dentistry: Progeroid Syndrome. A Case of Dental Management and Oral Rehabilitation

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