1,073 results match your criteria Cutis Laxa Elastolysis

Loss of zebrafish atp6v1e1b, encoding a subunit of vacuolar ATPase, recapitulates human ARCL type 2C syndrome and identifies multiple pathobiological signatures.

PLoS Genet 2021 Jun 18;17(6):e1009603. Epub 2021 Jun 18.

Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium.

The inability to maintain a strictly regulated endo(lyso)somal acidic pH through the proton-pumping action of the vacuolar-ATPases (v-ATPases) has been associated with various human diseases including heritable connective tissue disorders. Autosomal recessive (AR) cutis laxa (CL) type 2C syndrome is associated with genetic defects in the ATP6V1E1 gene and is characterized by skin wrinkles or loose redundant skin folds with pleiotropic systemic manifestations. The underlying pathological mechanisms leading to the clinical presentations remain largely unknown. Read More

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LTBP4 in Health and Disease.

Genes (Basel) 2021 May 23;12(6). Epub 2021 May 23.

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Latent transforming growth factor β (TGFβ)-binding protein (LTBP) 4, a member of the LTBP family, shows structural homology with fibrillins. Both these protein types are characterized by calcium-binding epidermal growth factor-like repeats interspersed with 8-cysteine domains. Based on its domain composition and distribution, LTBP4 is thought to adopt an extended structure, facilitating the linear deposition of tropoelastin onto microfibrils. Read More

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Normal transferrin patterns in congenital disorders of glycosylation with Golgi homeostasis disruption: apolipoprotein C-III at the rescue!

Clin Chim Acta 2021 Aug 20;519:285-290. Epub 2021 May 20.

AP-HP, Biochimie Métabolique et Cellulaire, Hôpital Bichat-Claude Bernard, Paris, France; INSERM UMR1193, Mécanismes cellulaires et moléculaires de l'adaptation au stress et cancérogenèse, Université Paris-Sud, Châtenay-Malabry, France. Electronic address:

We identified three cases of congenital disorders of glycosylation (CDG) with Golgi homeostasis disruption, one ATP6V0A2-CDG and two COG4-CDG, with normal transferrin screening analyses. Patient 1 (P1) presented at birth with cutis laxa. Patient 2 (P2) and patient 3 (P3) are adult siblings and presented with severe symptoms evocative of inborn errors of metabolism. Read More

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Bi-allelic premature truncating variants in LTBP1 cause cutis laxa syndrome.

Am J Hum Genet 2021 06 14;108(6):1095-1114. Epub 2021 May 14.

Center for Medical Genetics Ghent, Ghent University Hospital, Ghent 9000, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent 9000, Belgium. Electronic address:

Latent transforming growth factor β (TGFβ)-binding proteins (LTBPs) are microfibril-associated proteins essential for anchoring TGFβ in the extracellular matrix (ECM) as well as for correct assembly of ECM components. Variants in LTBP2, LTBP3, and LTBP4 have been identified in several autosomal recessive Mendelian disorders with skeletal abnormalities with or without impaired development of elastin-rich tissues. Thus far, the human phenotype associated with LTBP1 deficiency has remained enigmatic. Read More

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A novel GSN variant outside the G2 calcium-binding domain associated with Amyloidosis of the Finnish type.

Hum Mutat 2021 May 11. Epub 2021 May 11.

Flinders Department of Ophthalmology, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.

Gelsolin (GSN) variants have been implicated in amyloidosis of the Finnish type. This case series reports a novel GSN:c.1477T>C,p. Read More

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Clinical Features and Brain MRI Findings in Korean Patients with AGel Amyloidosis.

Yonsei Med J 2021 May;62(5):431-438

Department of Neurology, Rehabilitation Institute of Neuromuscular Disease, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: AGel amyloidosis is systemic amyloidosis caused by pathogenic variants in the GSN gene. In this study, we sought to characterize the clinical and brain magnetic resonance image (MRI) features of Korean patients with AGel amyloidosis.

Materials And Methods: We examined 13 patients with AGel amyloidosis from three unrelated families. Read More

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Severe congenital cutis laxa: Identification of novel homozygous LOX gene variants in two families.

Clin Genet 2021 Apr 18. Epub 2021 Apr 18.

Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Western Australia, Australia.

We report three babies from two families with a severe lethal form of congenital cutis laxa. All three had redundant and doughy-textured skin and two siblings from one family had facial dysmorphism. Echocardiograms showed thickened and poorly contractile hearts, arterial dilatation and tortuosity. Read More

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Loss-of-Function Variants in Cause a Recognizable Connective Tissue Disorder Characterized by Cutis Laxa and Multiple Herniations.

Genes (Basel) 2021 Mar 31;12(4). Epub 2021 Mar 31.

Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium.

Hereditary disorders of connective tissue (HDCT) compromise a heterogeneous group of diseases caused by pathogenic variants in genes encoding different components of the extracellular matrix and characterized by pleiotropic manifestations, mainly affecting the cutaneous, cardiovascular, and musculoskeletal systems. We report the case of a 9-year-old boy with a discernible connective tissue disorder characterized by cutis laxa (CL) and multiple herniations and caused by biallelic loss-of-function variants in . Hence, we identified as a novel disease-causing gene in the CL spectrum, differentiating it from other HDCT. Read More

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[Living with cutis laxa].

Rev Prat 2020 11;70(9):991-992

Association Cutis laxa internationale, Bons-en-Chablais (74), France.

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November 2020

Genetic analysis of Pycr1 and Pycr2 in mice.

Genetics 2021 May;218(1)

The Jackson Laboratory, Bar Harbor, ME 04609, USA.

The final step in proline biosynthesis is catalyzed by three pyrroline-5-carboxylate reductases, PYCR1, PYCR2, and PYCR3, which convert pyrroline-5-carboxylate (P5C) to proline. Mutations in human PYCR1 and ALDH18A1 (P5C Synthetase) cause Cutis Laxa (CL), whereas mutations in PYCR2 cause hypomyelinating leukodystrophy 10 (HLD10). Here, we investigated the genetics of Pycr1 and Pycr2 in mice. Read More

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SPG9A with the new occurrence of an ALDH18A1 mutation in a CMT1A family with PMP22 duplication: case report.

BMC Neurol 2021 Feb 11;21(1):64. Epub 2021 Feb 11.

Department of Neurology, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, 409-3898, Japan.

Background: ALDH18A1 mutations lead to delta-1-pyrroline-5-carboxylate-synthetase (P5CS) deficiency, which is a urea cycle-related disorder including SPG9A, SPG9B, autosomal dominant cutis laxa-3 (ADCL3), and autosomal recessive cutis laxa type 3A (ARCL3A). These diseases exhibit a broad clinical spectrum, which makes the diagnosis of P5CS deficiency difficult. We report here a rare Japanese family including both patients with an ALDH18A1 mutation (SPG9A) and ones with CMT1A. Read More

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February 2021

Bioenergetic analysis of aged-phenotype skin in a rare syndromic cutis laxa.

J Cosmet Dermatol 2021 Feb 1. Epub 2021 Feb 1.

Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

Background: Skin aging is an inevitable phenomenon characterized by wrinkled skin and loss of elasticity. To date, several studies have been performed on skin aging to discover the underlying mechanisms and improve efficient preventive strategies and anti-aging therapeutics.

Aims: Here, we aimed to investigate the modifications of oxidative phosphorylation and glycolysis which are the critical determinants of aging in aged-phenotype skin. Read More

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February 2021

New insight into clinical heterogeneity and inheritance diversity of FBLN5-related cutis laxa.

Orphanet J Rare Dis 2021 01 28;16(1):51. Epub 2021 Jan 28.

Department of Medical Genetics, Tabriz University of Medical Sciences, Tabriz, Iran.

Background: FBLN5-related cutis laxa (CL) is a rare disorder that involves elastic fiber-enriched tissues and is characterized by lax skin and variable systemic involvement such as pulmonary emphysema, arterial involvement, inguinal hernias, hollow viscus diverticula and pyloric stenosis. This type of CL follows mostly autosomal recessive (AR) and less commonly autosomal dominant patterns of inheritance.

Results: In this study, we detected a novel homozygous missense variant in exon 6 of FBLN5 gene (c. Read More

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January 2021

Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel Variant p.Glu580Lys.

Int J Mol Sci 2021 Jan 22;22(3). Epub 2021 Jan 22.

Eye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.

Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel variant p. Read More

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January 2021

Ehlers-Danlos Syndrome: Immunologic contrasts and connective tissue comparisons.

J Transl Autoimmun 2021 20;4:100077. Epub 2020 Dec 20.

Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA.

Ehlers-Danlos Syndrome (EDS) is a family of multisystemic hereditary connective tissue disorders now comprised of 13 recognized subtypes, classical, classical-like, cardiac-valvular, vascular, hypermobile, arthrochlasia, dermosparaxis, kyphoscoliotic, brittle cornea syndrome, spondylodysplastic, musculocontractural, myopathic, and periodontal, as designated by the most recent 2017 International classification system. Clinical presentation of this disease can range from mild manifestations including skin hyperextensibility and joint hypermobility, to more severe complications such as vascular and organ rupture. While there may be accompanying inflammation in some of the subtypes of EDS, the pathogenic mechanisms have not been clearly defined. Read More

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December 2020

Review of clinical and molecular variability in autosomal recessive cutis laxa 2A.

Am J Med Genet A 2021 03 27;185(3):955-965. Epub 2020 Dec 27.

Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy.

ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), is a subtype of hereditary cutis laxa originally characterized by skin, skeletal, and neurological involvement, and a combined defect of N-glycosylation and O-glycosylation. The associated clinical spectrum subsequently expanded to a less severe phenotype dominated by cutaneous involvement. At the moment, ARCL2A was described in a few case reports and series only. Read More

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A Novel Splice-Site Mutation in the Gene Suggests an Alternative Mechanism for Vascular Elastinopathies.

Appl Clin Genet 2020 17;13:233-240. Epub 2020 Dec 17.

Laboratorio de Biología Molecular y Pruebas Diagnósticas de Alta Complejidad, Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia.

The gene encodes elastin, a fundamental protein of the extracellular matrix that confers elasticity to different tissues including blood vessels. The formation of elastin fibers is a complex process involving monomer coacervation and subsequent crosslinking. Mutations in exons 1-29 of the gene have been linked to supravalvular aortic stenosis (SVAS) whereas mutations in exons 30-33 are associated with autosomal dominant cutis laxa (ADCL). Read More

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December 2020

A proposal of rehabilitative approach in the rare disease "De Barsy Syndrome": case report.

Clin Ter 2021 Jan-Feb;171(1):e4-e7

Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital-Sapienza University of Rome.

De Barsy syndrome is an autosomal recessive condition characterized by an progeroid appearance with distinctive facial features and cutis laxa. Ophthalmological, orthopedic, and neurological anomalies are generally also present. This syndrome is rare and the complex therapeutic management, from a surgical but also rehabilitative point of view, has not been recognized. Read More

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Expanding the clinical and molecular spectrum of ATP6V1A related metabolic cutis laxa.

J Inherit Metab Dis 2020 Dec 15. Epub 2020 Dec 15.

Institut für Medizinische Genetik und Humangenetik, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Several inborn errors of metabolism show cutis laxa as a highly recognizable feature. One group of these metabolic cutis laxa conditions is autosomal recessive cutis laxa type 2 caused by defects in v-ATPase components or the mitochondrial proline cycle. Besides cutis laxa, muscular hypotonia and cardiac abnormalities are hallmarks of autosomal recessive cutis laxa type 2D (ARCL2D) due to pathogenic variants in ATP6V1A encoding subunit A of the v-ATPase. Read More

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December 2020

Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type IC and a review of the related literature.

BMC Med Genomics 2020 12 10;13(1):183. Epub 2020 Dec 10.

Laboratory of Genetic and Metabolism, Department of Paediatric Endocrine and Metabolism, Maternal and Child Health Hospital of Guangxi, Nanning, 530000, China.

Background: Autosomal recessive cutis laxa type IC (ARCL IC, MIM: #613177) results from a mutation in the LTBP4 gene (MIM: #604710) on chromosome 19q13.

Case Presentation: A 28-day-old Chinese infant with generalized cutis laxa accompanied by impaired pulmonary, gastrointestinal, genitourinary, retinal hemorrhage, abnormality of coagulation and hyperbilirubinemia was admitted to our hospital. To find out the possible causes of these symptoms, whole-exome sequencing was performed on the infant. Read More

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December 2020

Expanding the PURA syndrome phenotype: A child with the recurrent PURA p.(Phe233del) pathogenic variant showing similarities with cutis laxa.

Mol Genet Genomic Med 2021 01 4;9(1):e1562. Epub 2020 Dec 4.

Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Background: PURA syndrome is rare autosomal dominant condition characterized by moderate to severe neurodevelopmental delay with absence of speech in nearly all patients and lack of independent ambulation in many. Early-onset problems include excessive hiccups, hypotonia, hypersomnolence, hypothermia, feeding difficulties, recurrent apneas, epileptic seizures, and abnormal nonepileptic movements. Other less common manifestations comprise congenital heart defects, urogenital malformations, and various skeletal, ophthalmological, gastrointestinal, and endocrine anomalies. Read More

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January 2021

Pulmonary Manifestations of Skin Disorders in Children.

Pediatr Clin North Am 2021 02;68(1):261-276

Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA.

Systemic diseases often manifest with cutaneous findings. Many pediatric conditions with prominent skin findings also have significant pulmonary manifestations. These conditions include both inherited multisystem genetic disorders such as yellow-nail syndrome, neurofibromatosis type 1, tuberous sclerosis complex, hereditary hemorrhagic telangiectasia, Klippel-Trénaunay-Weber syndrome, cutis laxa, Ehlers-Danlos syndrome, dyskeratosis congenita, reactive processes such as mastocytosis, and aquagenic wrinkling of the palms. Read More

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February 2021

ATP7A mutation with occipital horns and distal motor neuropathy: A continuum.

Eur J Med Genet 2020 Dec 31;63(12):104087. Epub 2020 Oct 31.

Service de génétique, CLAD Ouest, CHU Rennes, Rennes, France; Service de génétique, CRDI, CHU Rennes, Rennes, France.

ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489) (Kennerson et al., 2010). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein (Møller, 2015). Read More

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December 2020

Successful treatment of acquired cutis laxa with urticarial eruption by diphenyl sulfone.

Clin Exp Dermatol 2021 Apr 15;46(3):599-603. Epub 2020 Oct 15.

Dermatology Hospital, Southern Medical University, Guangdong, China.

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Cutis laxa: A comprehensive overview of clinical characteristics and pathophysiology.

Clin Genet 2021 Jan 27;99(1):53-66. Epub 2020 Oct 27.

Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium.

Cutis laxa (CL) syndromes comprise a rare group of multisystem disorders that share loose redundant skin folds as hallmark clinical feature. CL results from impaired elastic fiber assembly and homeostasis, and the known underlying gene defects affect different extracellular matrix proteins, intracellular trafficking, or cellular metabolism. Due to the underlying clinical and molecular heterogeneity, the diagnostic work-up of CL patients is often challenging. Read More

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January 2021

Six-year follow-up of a survivor of cervical spine fracture and dislocation with oesophageal perforation following long scarf syndrome - a case report and literature review.

BMC Musculoskelet Disord 2020 Oct 14;21(1):677. Epub 2020 Oct 14.

Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, No 95 Yongan Road Xicheng District, Beijing, 100050, China.

Background: Accidental strangulation due to scarf getting caught in the wheels of a vehicle or machine was called "Isadora Duncan Syndrome" or "Long Scarf Syndrome". Survival of concomitant fracture dislocation of cervical spine and oesophageal perforation following Long Scarf Syndrome was rarely described and medium-term follow-up for this lesion has not been reported.

Case Presentation: We present a 39-year-old female who suffered accidental strangulation caused by the scarf around her neck getting trapped in the wheels of the a vehicle and was referred to our hospital forty days post injury. Read More

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October 2020

Dysregulated assembly of elastic fibers in fibulin-5 knockout mice results in a tendon-specific increase in elastic modulus.

J Mech Behav Biomed Mater 2021 01 7;113:104134. Epub 2020 Oct 7.

Department of Biomedical Engineering, Washington University in St. Louis, USA; Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, USA; Department of Orthopaedic Surgery, Washington University in St. Louis, USA. Electronic address:

Elastic fiber assembly is coordinated in part by fibulin-5, a matricellular protein. When fibulin-5 is not available to guide elastogenesis, elastin forms into disconnected globules instead of the dense elastic fiber core found in healthy tissues. Despite the growing evidence for a significant role of elastic fibers in tendon mechanics and the clinical relevance to cutis laxa, a human disease which can be caused by a mutation in the gene encoding fibulin-5, it is unknown how malformed elastic fibers affect tendon function. Read More

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January 2021