Mariana Aracena - Academia.edu (original) (raw)
Papers by Mariana Aracena
Clinical Pediatrics, 1982
Two infants, born with extensive abnormalities probably resulting from maternal use of alcohol an... more Two infants, born with extensive abnormalities probably resulting from maternal use of alcohol and hydantoin during pregnancy, are described. The findings suggest the speculation that con current exposure to these teratogens, in utero, may have synergistic or additive effects upon a fetus, producing serious malformations. The purpose of this report is to alert physicians to this combined syndrome. Its occurrence may be more common than anticipated.
Neuromuscular Disorders, 2007
Revista chilena de pediatría, Mar 1, 2000
Nephropathy caused by cystinosis is a rare recessive disorder produced by a defect in the lysosom... more Nephropathy caused by cystinosis is a rare recessive disorder produced by a defect in the lysosomal transport of cysteine. This results in intracellular crystal deposits in the kidneys, cornea and other tissues. It constitutes the commonest congenital cause of Fanconi's syndrome and progresses during the first decade of life to chronic renal failure. The diagnosis is confirmed by the detection of cystine in circulating leucocytes and lymphoblasts. The treatment consists in replacing the losses caused by the tubular defect and the oral administration of cystamine which depletes cystine and favours its transport across the lysosomal membrane. The objective of this report is to present the first case of cystinosis diagnosed and treated in Chile. The patient was hospitalized at the age of 15 months with advanced disnutrition, clinical rickets, severe dehydration, hypokalaemia, hypophosphataemia, metabolic acidosis consistent with Fanconi's syndrome. An elevated concentration of cystine was found in the polymorphic leucocytes confirming the diagnosis. After 2 years of treatment with oral cystamine the patient demonstrates an excellent evolution with regards to stature and conservation of renal function, although the tubular defect persists.
American Journal of Medical Genetics, May 30, 2019
We report the case of a 14 years and 8 months girl, who is the first child of nonconsanguineous p... more We report the case of a 14 years and 8 months girl, who is the first child of nonconsanguineous parents, with short stature, obstructive hypertrophic cardiomyopathy, multiple facial lentigines, high and wide forehead, downslanting palpebral fissures, low‐set ears, short neck, and pectus excavatum; all features suggestive of Noonan syndrome with multiple lentigines (NSML). In addition, the patient exhibited craniosynostosis. Molecular analysis of rats sarcoma (RAS)/mitogen‐activated protein kinase (MAPK) pathway genes with high‐resolution melting curve analysis followed by sequencing showed a RAF1 amino acid substitution of valine to glycine at position 263 (p.V263G). The present report provides clinical data regarding the first association of a RAF1 variant and craniosynostosis in a patient with clinical diagnosis of NSML.
Journal of Ultrasound in Medicine, Oct 1, 1999
In 1970, Aarskog described a rare X-linked developmental disorder characterized by short stature ... more In 1970, Aarskog described a rare X-linked developmental disorder characterized by short stature in association with a variety of structural anomalies involving mainly the face, distal extremities, and external genitalia (faciodigitogenital syndrome). 1 The major facial manifestations of this syndrome include hypertelorism, broad forehead, broad nasal bridge, short nose with anteverted nostrils, long philtrum, widow's peak hair anomaly, and ocular and ear anomalies. 1-3 Limb abnormalities consist of short broad hands, brachydactyly, interdigital webbing, hypoplasia of the middle phalanges, proximal interphalangeal joint laxity with concomitant flexion and restriction of movement of distal interphalangeal joints, and flat broad feet with bulbous toes. 1-3 Genital anomalies are characteristics and include shawl scrotum, cryptorchidism, and inguinal hernia. 1-3 Most affected patients have normal intelligence, but some authors have noted mild neurodevelopmental delay in up to 30% of the cases. 4
Revista Medica De Chile, Mar 1, 2003
We report a female newborn with type II mucolipidoses. This condition is characterized clinically... more We report a female newborn with type II mucolipidoses. This condition is characterized clinically by Hurler like features, progressive psychomotor retardation and death during the first or second year of life. Most cases present during the first year of life, with poor weight gain and coarse facies features. The cause of this rare autosomal recessive hereditary disease is the deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase, required for the synthesis of mannose-6-phosphate, the ligand that allows the transport of acid hydrolases into lysosomes. The patient had clinical features commonly found in mucolipidosis II, including disproportionate dwarfism, retarded psychomotor development, coarse facies features, gibbous and restricted joint mobility. The diagnosis was proved by an extremely elevated activity of lysosomal enzymes in the serum, secondary to non-regulated secretion and subsequent intracellular depletion of these proteins. The child suffered recurrent pneumonia and died at 22 months of age (Rev Med Chile 2003; 131: 314-9).
Revista chilena de pediatría, Jul 1, 2004
... Manejo de Síndromes malformativos. Mariana Aracena A. 1. ... [ Links ] 10.- Stamoyannou L,Kar... more ... Manejo de Síndromes malformativos. Mariana Aracena A. 1. ... [ Links ] 10.- Stamoyannou L,Karachaliou F, Neou P, Papataxiarchou K, Pistevos G, Bartsocas CS: Growth and growth hormone therapy in children with achondroplasia: a two-year experience. ...
Biology of Blood and Marrow Transplantation, Mar 1, 2018
Revista chilena de pediatría, Dec 1, 2012
Consentimiento informado de fotografías clínicas: presentado conforme. Este trabajo cumple con lo... more Consentimiento informado de fotografías clínicas: presentado conforme. Este trabajo cumple con los requisitos sobre consentimiento /asentimiento informado, comité de ética, financiamiento, estudios animales y sobre la ausencia de conflictos de intereses según corresponda.
Revista chilena de pediatría, Jul 1, 2003
American Journal of Medical Genetics, Sep 9, 2011
Revista chilena de pediatría, 1994
Revista médica de Chile, 1990
We evaluated the role of oxygen free radicals in the induction of acute stress gastric ulcer in r... more We evaluated the role of oxygen free radicals in the induction of acute stress gastric ulcer in rats. After 12 hr of immobility, ulcers of up to 4 mm were observed in the gastric mucosa. Pretreatment with allopurinol, a xanthine oxidase inhibitor, produced a significant reduction in the number and size of lesions (p < 0.0001). No protection was afforded by aluminum hydroxide or ranitidine alone, but enhanced protection was observed when given in association to allopurinol. A secondary role for H ions is suggested by these findings. Our results support the hypothesis of a role of oxygen free radicals in the pathogenesis of stress gastric ulcers. Allopurinol might be used in conditions predisposing to stress in patients.
Molecular Syndromology, Nov 29, 2017
Proximal 6q deletion is relatively uncommon. Prior to the introduction of chromosome microarrays,... more Proximal 6q deletion is relatively uncommon. Prior to the introduction of chromosome microarrays, 9 cases were described with deletions between 6q11 and 6q16 [Kumar et al., 1997]. The authors stated a variable degree of cognitive impairment associated with a recurrent distinctive facial phenotype, including upslanting palpebral fissures with epicanthal folds, a short nose with anteverted nares, long philtrum, thin lips, and large ears. Joint hypermobility and hernias were frequent. In this study, we describe a patient with a large deletion of the long arm in chromosome 6 (6q12q14.3), who has a phenotype consistent with Toriello-Carey syndrome (TCS). TCS is a genetically heterogeneous disorder originally described in 1988 in 4 patients [Toriello and Carey, 1988]. Key features include postnatal growth failure, hypotonia, developmental delay, intellectual disability, a short neck, and characteristic facial anomalies (hypertelorism/telecanthus, blepharophimosis, abnormal ears, small nose, full cheeks, thin lips, and micrognathia). Abnormal corpus callosum, laryngeal/tracheal anomalies, cardiovascular disease, herniae, genital anomalies in males, and skeletal defects have also been reported features [Toriello et al., 2003]. Prenatal sonographic findings
Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorpor... more Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the “diagnostic odyssey” for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international collaboration with Baylor College of Medicine, and the local development was structured as a hybrid model, where clinical and bioinformatics analysis were performed in-house and sequencing outsourced abroad, due to lack of high-throughput equipment in Chile. ...
Molecular syndromology, 2017
Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have dele... more Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have deletions of different sizes but share partial overlap and present with similar clinical features, and some of them were described prior to the introduction of chromosome microarrays. We describe a male patient with prenatal sonographic findings of nuchal edema, intrauterine growth restriction, renal pelvis dilatation, and oligohydramnios. At birth, facial dysmorphism, retro/micrognathia, a short and wide neck as well as cardiovascular and renal anomalies were noted. His clinical evolution has been marked by failure to thrive, severe developmental delay, and cognitive impairment. The diagnosis of Toriello-Carey syndrome (TCS) was based on his "gestalt." aCGH identified a de novo proximal deletion of 17 Mb in 6q (6q12q14.3). Deletion 6q13q14 seems to be responsible for the main facial features and should be considered within the differential diagnosis of TCS.
American journal of human genetics, Jan 2, 2017
Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of c... more Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of collagens, fibrillin-1, and other proteins. It is also known to play roles in skeletal tissues through its secretion by osteoblasts, chondrocytes, and mesenchymal cells. Spondylometaphyseal dysplasias (SMDs) comprise a diverse group of skeletal dysplasias and often manifest as short stature, growth-plate irregularities, and vertebral anomalies, such as scoliosis. By comparing the exomes of individuals with SMD with the radiographic appearance of "corner fractures" at metaphyses, we identified three individuals with fibronectin (FN1) variants affecting highly conserved residues. Furthermore, using matching tools and the SkelDys emailing list, we identified other individuals with de novo FN1 variants and a similar phenotype. The severe scoliosis in most individuals and rare developmental coxa vara distinguish individuals with FN1 mutations from those with classical Sutcliffe-type ...
Clinical Pediatrics, 1982
Two infants, born with extensive abnormalities probably resulting from maternal use of alcohol an... more Two infants, born with extensive abnormalities probably resulting from maternal use of alcohol and hydantoin during pregnancy, are described. The findings suggest the speculation that con current exposure to these teratogens, in utero, may have synergistic or additive effects upon a fetus, producing serious malformations. The purpose of this report is to alert physicians to this combined syndrome. Its occurrence may be more common than anticipated.
Neuromuscular Disorders, 2007
Revista chilena de pediatría, Mar 1, 2000
Nephropathy caused by cystinosis is a rare recessive disorder produced by a defect in the lysosom... more Nephropathy caused by cystinosis is a rare recessive disorder produced by a defect in the lysosomal transport of cysteine. This results in intracellular crystal deposits in the kidneys, cornea and other tissues. It constitutes the commonest congenital cause of Fanconi's syndrome and progresses during the first decade of life to chronic renal failure. The diagnosis is confirmed by the detection of cystine in circulating leucocytes and lymphoblasts. The treatment consists in replacing the losses caused by the tubular defect and the oral administration of cystamine which depletes cystine and favours its transport across the lysosomal membrane. The objective of this report is to present the first case of cystinosis diagnosed and treated in Chile. The patient was hospitalized at the age of 15 months with advanced disnutrition, clinical rickets, severe dehydration, hypokalaemia, hypophosphataemia, metabolic acidosis consistent with Fanconi's syndrome. An elevated concentration of cystine was found in the polymorphic leucocytes confirming the diagnosis. After 2 years of treatment with oral cystamine the patient demonstrates an excellent evolution with regards to stature and conservation of renal function, although the tubular defect persists.
American Journal of Medical Genetics, May 30, 2019
We report the case of a 14 years and 8 months girl, who is the first child of nonconsanguineous p... more We report the case of a 14 years and 8 months girl, who is the first child of nonconsanguineous parents, with short stature, obstructive hypertrophic cardiomyopathy, multiple facial lentigines, high and wide forehead, downslanting palpebral fissures, low‐set ears, short neck, and pectus excavatum; all features suggestive of Noonan syndrome with multiple lentigines (NSML). In addition, the patient exhibited craniosynostosis. Molecular analysis of rats sarcoma (RAS)/mitogen‐activated protein kinase (MAPK) pathway genes with high‐resolution melting curve analysis followed by sequencing showed a RAF1 amino acid substitution of valine to glycine at position 263 (p.V263G). The present report provides clinical data regarding the first association of a RAF1 variant and craniosynostosis in a patient with clinical diagnosis of NSML.
Journal of Ultrasound in Medicine, Oct 1, 1999
In 1970, Aarskog described a rare X-linked developmental disorder characterized by short stature ... more In 1970, Aarskog described a rare X-linked developmental disorder characterized by short stature in association with a variety of structural anomalies involving mainly the face, distal extremities, and external genitalia (faciodigitogenital syndrome). 1 The major facial manifestations of this syndrome include hypertelorism, broad forehead, broad nasal bridge, short nose with anteverted nostrils, long philtrum, widow's peak hair anomaly, and ocular and ear anomalies. 1-3 Limb abnormalities consist of short broad hands, brachydactyly, interdigital webbing, hypoplasia of the middle phalanges, proximal interphalangeal joint laxity with concomitant flexion and restriction of movement of distal interphalangeal joints, and flat broad feet with bulbous toes. 1-3 Genital anomalies are characteristics and include shawl scrotum, cryptorchidism, and inguinal hernia. 1-3 Most affected patients have normal intelligence, but some authors have noted mild neurodevelopmental delay in up to 30% of the cases. 4
Revista Medica De Chile, Mar 1, 2003
We report a female newborn with type II mucolipidoses. This condition is characterized clinically... more We report a female newborn with type II mucolipidoses. This condition is characterized clinically by Hurler like features, progressive psychomotor retardation and death during the first or second year of life. Most cases present during the first year of life, with poor weight gain and coarse facies features. The cause of this rare autosomal recessive hereditary disease is the deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase, required for the synthesis of mannose-6-phosphate, the ligand that allows the transport of acid hydrolases into lysosomes. The patient had clinical features commonly found in mucolipidosis II, including disproportionate dwarfism, retarded psychomotor development, coarse facies features, gibbous and restricted joint mobility. The diagnosis was proved by an extremely elevated activity of lysosomal enzymes in the serum, secondary to non-regulated secretion and subsequent intracellular depletion of these proteins. The child suffered recurrent pneumonia and died at 22 months of age (Rev Med Chile 2003; 131: 314-9).
Revista chilena de pediatría, Jul 1, 2004
... Manejo de Síndromes malformativos. Mariana Aracena A. 1. ... [ Links ] 10.- Stamoyannou L,Kar... more ... Manejo de Síndromes malformativos. Mariana Aracena A. 1. ... [ Links ] 10.- Stamoyannou L,Karachaliou F, Neou P, Papataxiarchou K, Pistevos G, Bartsocas CS: Growth and growth hormone therapy in children with achondroplasia: a two-year experience. ...
Biology of Blood and Marrow Transplantation, Mar 1, 2018
Revista chilena de pediatría, Dec 1, 2012
Consentimiento informado de fotografías clínicas: presentado conforme. Este trabajo cumple con lo... more Consentimiento informado de fotografías clínicas: presentado conforme. Este trabajo cumple con los requisitos sobre consentimiento /asentimiento informado, comité de ética, financiamiento, estudios animales y sobre la ausencia de conflictos de intereses según corresponda.
Revista chilena de pediatría, Jul 1, 2003
American Journal of Medical Genetics, Sep 9, 2011
Revista chilena de pediatría, 1994
Revista médica de Chile, 1990
We evaluated the role of oxygen free radicals in the induction of acute stress gastric ulcer in r... more We evaluated the role of oxygen free radicals in the induction of acute stress gastric ulcer in rats. After 12 hr of immobility, ulcers of up to 4 mm were observed in the gastric mucosa. Pretreatment with allopurinol, a xanthine oxidase inhibitor, produced a significant reduction in the number and size of lesions (p < 0.0001). No protection was afforded by aluminum hydroxide or ranitidine alone, but enhanced protection was observed when given in association to allopurinol. A secondary role for H ions is suggested by these findings. Our results support the hypothesis of a role of oxygen free radicals in the pathogenesis of stress gastric ulcers. Allopurinol might be used in conditions predisposing to stress in patients.
Molecular Syndromology, Nov 29, 2017
Proximal 6q deletion is relatively uncommon. Prior to the introduction of chromosome microarrays,... more Proximal 6q deletion is relatively uncommon. Prior to the introduction of chromosome microarrays, 9 cases were described with deletions between 6q11 and 6q16 [Kumar et al., 1997]. The authors stated a variable degree of cognitive impairment associated with a recurrent distinctive facial phenotype, including upslanting palpebral fissures with epicanthal folds, a short nose with anteverted nares, long philtrum, thin lips, and large ears. Joint hypermobility and hernias were frequent. In this study, we describe a patient with a large deletion of the long arm in chromosome 6 (6q12q14.3), who has a phenotype consistent with Toriello-Carey syndrome (TCS). TCS is a genetically heterogeneous disorder originally described in 1988 in 4 patients [Toriello and Carey, 1988]. Key features include postnatal growth failure, hypotonia, developmental delay, intellectual disability, a short neck, and characteristic facial anomalies (hypertelorism/telecanthus, blepharophimosis, abnormal ears, small nose, full cheeks, thin lips, and micrognathia). Abnormal corpus callosum, laryngeal/tracheal anomalies, cardiovascular disease, herniae, genital anomalies in males, and skeletal defects have also been reported features [Toriello et al., 2003]. Prenatal sonographic findings
Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorpor... more Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the “diagnostic odyssey” for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international collaboration with Baylor College of Medicine, and the local development was structured as a hybrid model, where clinical and bioinformatics analysis were performed in-house and sequencing outsourced abroad, due to lack of high-throughput equipment in Chile. ...
Molecular syndromology, 2017
Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have dele... more Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have deletions of different sizes but share partial overlap and present with similar clinical features, and some of them were described prior to the introduction of chromosome microarrays. We describe a male patient with prenatal sonographic findings of nuchal edema, intrauterine growth restriction, renal pelvis dilatation, and oligohydramnios. At birth, facial dysmorphism, retro/micrognathia, a short and wide neck as well as cardiovascular and renal anomalies were noted. His clinical evolution has been marked by failure to thrive, severe developmental delay, and cognitive impairment. The diagnosis of Toriello-Carey syndrome (TCS) was based on his "gestalt." aCGH identified a de novo proximal deletion of 17 Mb in 6q (6q12q14.3). Deletion 6q13q14 seems to be responsible for the main facial features and should be considered within the differential diagnosis of TCS.
American journal of human genetics, Jan 2, 2017
Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of c... more Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of collagens, fibrillin-1, and other proteins. It is also known to play roles in skeletal tissues through its secretion by osteoblasts, chondrocytes, and mesenchymal cells. Spondylometaphyseal dysplasias (SMDs) comprise a diverse group of skeletal dysplasias and often manifest as short stature, growth-plate irregularities, and vertebral anomalies, such as scoliosis. By comparing the exomes of individuals with SMD with the radiographic appearance of "corner fractures" at metaphyses, we identified three individuals with fibronectin (FN1) variants affecting highly conserved residues. Furthermore, using matching tools and the SkelDys emailing list, we identified other individuals with de novo FN1 variants and a similar phenotype. The severe scoliosis in most individuals and rare developmental coxa vara distinguish individuals with FN1 mutations from those with classical Sutcliffe-type ...