Caveolar Dysfunction and Lipodystrophies

Congenital generalized lipodystrophy (CGL) is a rare, heterogeneous, autosomal recessive disorder characterized by near total absence of body fat with increased muscularity noticed at birth or in early infancy. Four distinct genetic subtypes of CGL have been reported to date. Types 1 and 2 are caused by biallelic variants in the 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) genes, respectively, and are the most common subtypes (1). Types 3 and 4 are extremely rare and are caused by biallelic variants in the caveolin 1 (CAV1) (2), and Caveolae Associated Protein-1 (CAVIN1; also known as polymerase I and transcript release factor (PTRF)]) genes (3), respectively. Patients with all CGL subtypes are predisposed to metabolic complications of insulin resistance, such as diabetes mellitus, hypertriglyceridemia and hepatic steatosis; however, each subtype presents with some unique clinical features.

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Importance of Immediate Thiamine Therapy in Children with Suspected Thiamine-Responsive Megaloblastic Anemia—Report on Two Patients Carrying a Novel SLC19A2 Gene Mutation

Journal of Pediatric Genetics ◽

10.1055/s-0040-1717136 ◽

2020 ◽

Author(s):

Anita Spehar Uroic ◽

Dragan Milenkovic ◽

Elisa De Franco ◽

Ernest Bilic ◽

Natasa Rojnic Putarek ◽

...

Keyword(s):

Diabetes Mellitus ◽

Autosomal Recessive ◽

Megaloblastic Anemia ◽

Sensorineural Deafness ◽

Autosomal Recessive Disorder ◽

Missense Variant ◽

Severe Anemia ◽

Thiamine Therapy ◽

Compound Heterozygotes ◽

Slc19a2 Gene

AbstractThiamine-responsive megaloblastic anemia (TRMA) is an autosomal recessive disorder characterized by the development of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. We report on the first two Croatian patients with TRMA, compound heterozygotes for nonsense, c.373C > T; p.(Gln125Ter) and novel missense variant, c.1214C > G; p.(Thr405Arg) in SLC19A2 gene. The first was diagnosed at 4 months with diabetes mellitus and severe anemia requiring transfusions. As TRMA was suspected, thiamine therapy was immediately started to prevent further transfusions and insulin therapy. His brother developed extreme anemia at 3 weeks of age while waiting for the results of the genetic test. Severe anemia in this sibling may have been prevented if thiamine had been initiated earlier.

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Caveolin-1 Induces Formation of Membrane Tubules That Sense Actomyosin Tension and Are Inhibited by Polymerase I and Transcript Release Factor/Cavin-1

Molecular Biology of the Cell ◽

10.1091/mbc.e09-05-0417 ◽

2010 ◽

Vol 21 (13) ◽

pp. 2226-2240 ◽

Cited By ~ 20

Author(s):

Prakhar Verma ◽

Anne G. Ostermeyer-Fay ◽

Deborah A. Brown

Keyword(s):

Cancer Cells ◽

Actin Filaments ◽

Release Factor ◽

Cortical Actin ◽

Functional Interaction ◽

Tubule Formation ◽

Normal Cells ◽

Caveolin 1 ◽

Membrane Tubules ◽

Polymerase I

Caveolin-1 and caveolae are often lost in cancer. We found that levels of caveolin-1 and polymerase I and transcript release factor (PTRF)/cavin-1 correlated closely in a panel of cancer and normal cells. Caveolin-1 reexpression in cancer cells lacking both proteins induced formation of long membrane tubules rarely seen in normal cells. PTRF/cavin-1 inhibited tubule formation when coexpressed with caveolin-1 in these cells, whereas suppression of PTRF/cavin-1 expression in cells that normally expressed both genes stimulated tubule formation by endogenous caveolin-1. Caveolin-1 tubules shared several features with previously described Rab8 tubules. Coexpressed Rab8 and caveolin-1 labeled the same tubules (as did EHD proteins), and synergized to promote tubule formation, whereas a dominant-interfering Rab8 mutant inhibited caveolin-1 tubule formation. Both overexpression and inhibition of dynamin-2 reduced the abundance of caveolin-1 tubules. Caveolin-1 reexpression in SK-BR-3 breast cancer cells also induced formation of short membrane tubules close to cortical actin filaments, which required actin filaments but not microtubules. Actomyosin-induced tension destabilized both long and short tubules; they often snapped and resolved to small vesicles. Actin filament depolymerization or myosin II inhibition reduced tension and stabilized tubules. These data demonstrate a new function for PTRF/cavin-1, a new functional interaction between caveolin-1 and Rab8 and that actomyosin interactions can induce tension on caveolin-1-containing membranes.

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Bardet-Biedl Syndrome: A Case Report

BIRDEM Medical Journal ◽

10.3329/birdem.v8i2.36661 ◽

2018 ◽

Vol 8 (2) ◽

pp. 184-186

Author(s):

Miah Wahiduzzaman ◽

Muhammad Abdur Rahim ◽

Mahboob Iftekhar

Keyword(s):

Diabetes Mellitus ◽

Congenital Heart Disease ◽

Congenital Heart ◽

Autosomal Recessive ◽

Learning Difficulties ◽

Clinical Manifestations ◽

Autosomal Recessive Disorder ◽

Cone Dystrophy ◽

Bardet Biedl Syndrome ◽

Development Delay

Bardet-Beidl syndrome is a rare autosomal recessive disorder having heterogeneous clinical manifestations including rod-cone dystrophy, polydactyly, obesity, learning difficulties, development delay, speech deficit, diabetes mellitus, congenital heart disease etc. Most of these symptoms are not present at birth but appear and progressively worsen during the first and second decades of life. The combined occurrence of diabetes mellitus and retinitis pigmentosa is rare. Here, we present such a case.Birdem Med J 2018; 8(2): 184-186

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Clinical Significance of the Fetuin-A-to-Adiponectin Ratio in Obese Children and Adolescents with Diabetes Mellitus

Children ◽

10.3390/children8121155 ◽

2021 ◽

Vol 8 (12) ◽

pp. 1155

Author(s):

Moon-Bae Ahn ◽

Seul-Ki Kim ◽

Shin-Hee Kim ◽

Won-Kyoung Cho ◽

Jin-Soon Suh ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Children And Adolescents ◽

Cell Function ◽

Obese Children ◽

Metabolic Complications ◽

Fetuin A ◽

Diabetic Children ◽

Β Cell Function

Fetuin-A and adiponectin are inflammatory cytokines associated with obesity and insulin resistance. This study aimed to examine the fetuin-A-to-adiponectin ratio (FAR) in diabetic children and to determine the role of FAR. A total of 54 children and adolescents with diabetes mellitus (DM) and 44 controls aged 9–16 years were included in this study. Clinical characteristics, including plasma fetuin-A and adiponectin levels, were compared with respect to body mass index (BMI) and diabetes type. Of 98 children, 54.1% were obese, whereas 18.4% were obese and diabetic. FAR was higher in obese children with DM than in non-obese children and also in type 2 DM children than in type 1. FAR showed a stronger association with BMI than with fetuin-A and adiponectin individually, and its association was more prominent in diabetic children than in controls. BMI was a risk factor for increased FAR. Plasma fetuin-A was elevated in obese children, and its association with insulin resistance and β cell function seemed more prominent in diabetic children after adjustment for adiponectin. Thus, FAR could be a useful surrogate for the early detection of childhood metabolic complications in diabetic children, particularly those who are obese.

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Laurence -Moon-Bardet- Biedl syndrome with Diabetes Mellitus

Journal of Medicine ◽

10.3329/jom.v13i1.10083 ◽

1970 ◽

Vol 13 (1) ◽

pp. 97-99

Author(s):

Monzoor Quader ◽

Mohammad Syedul Islam ◽

Quazi Mamatz Uddin Ahmed ◽

Md Abul Kalam Azad ◽

Md Abdur Rahim

Keyword(s):

Diabetes Mellitus ◽

Renal Cell Carcinoma ◽

Mental Retardation ◽

Central Obesity ◽

Autosomal Recessive ◽

Autosomal Recessive Disorder ◽

Cone Dystrophy ◽

Learning Difficulty ◽

Bardet Biedl Syndrome ◽

Increased Risk

A 13 year old boy presented with obesity, reduced vision, mental retardation, hypogonadism, delayed development and learning difficulty. On examination, he had polydactyly, moon face, bilateral gynaecomastia, small penis and testis. Retinitis pigmentosa was found on fundoscopy. With these typical features, he was diagnosed as a case of Laurence-Moon-Bardet-Beidle syndrome. It is a rare autosomal recessive disorder with mutation in 6 loci identified so far. It is commonly found in communities with high inter-family marriage. Clinical features appear early in childhood and diagnosis is usually done by puberty. Prominent features include rod-cone dystrophy leading to blindness, postaxial polydactyly, central obesity, learning disability, hypogonadism in males, renal dysfunction with increased risk for renal cell carcinoma. DOI: http://dx.doi.org/10.3329/jom.v13i1.10083 JOM 2012; 13(1): 97-99

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Three Cases of Joubert Syndrome in a Consanguineous Syrian Family and a Interesting Case of Multinational Collaboration

Journal of Pediatric Genetics ◽

10.1055/s-0040-1721826 ◽

2021 ◽

Author(s):

Davor Petrović ◽

Vida Čulić ◽

Zofia Swinderek-Alsayed

Keyword(s):

Low Income ◽

Autosomal Recessive ◽

Autosomal Recessive Disorder ◽

Joubert Syndrome ◽

Interesting Case ◽

Low Income Countries ◽

Ocular Motor ◽

Quality Health Care ◽

Quality Health ◽

Motor Apraxia

AbstractJoubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.

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A Case of Congenital Glucose Galactose Malabsorption with a New Mutation in the SLC5A1 Gene

Journal of Pediatric Genetics ◽

10.1055/s-0040-1719161 ◽

2020 ◽

Author(s):

Hasan Akduman ◽

Dilek Dilli ◽

Serdar Ceylaner

Keyword(s):

Mutation Analysis ◽

Autosomal Recessive ◽

Glucose Transporter ◽

Neonatal Period ◽

Autosomal Recessive Disorder ◽

Homozygous Mutation ◽

New Mutation ◽

Early Neonatal Period ◽

Sodium Dependent ◽

Hypernatremic Dehydration

AbstractCongenital glucose-galactose malabsorption (CGGM) is an autosomal recessive disorder originating from an abnormal transporter mechanism in the intestines. It was sourced from a mutation in the SLC5A1 gene, which encodes a sodium-dependent glucose transporter. Here we report a 2-day-old girl with CGGM who presented with severe hypernatremic dehydration due to diarrhea beginning in the first hours of life. Mutation analysis revealed a novel homozygous mutation NM_000343.3 c.127G > A (p.Gly43Arg) in the SLC5A1 gene. Since CGGM can cause fatal diarrhea in the early neonatal period, timely diagnosis of the disease seems to be essential.

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