Primary distal renal tubular acidosis (dRTA) or Type 1 RTA in children is caused by a genetic defect (involved genes ATP6V0A4 , ATP6V1B1 , SLC4A1 , FOXI1 , or WDR72 ), which causes tubular transport defects characterized by an inability to appropriately acidify urine with resultant persistent hyperchloremic metabolic acidosis. Retrospective analysis of 28 children (14 males) under the age of 14 years with dRTA seen from 2010 to 2019 was reviewed, and detailed clinic records were analyzed. The clinical features, investigations, and response to treatment were recorded. The median age of the children at presentation was 30 months (range: 9.25-72 months), and the median age at onset of symptoms was 2 months. All the children had growth failure, polyuria, and polydipsia at presentation. Mean serum potassium, pH, bicarbonate, and anion gap at presentation was 2.3 ± 0.5 mmol/L, 7.22 ± 0.09, 13.28 ± 4.37 mmol/L, and 9.3 ± 2.18, respectively. Mean serum potassium, pH, bicarbonate at follow-up was 3.88 ± 0.6 mmol/L, 7.35 ± 0.06, and 20.13 ± 4.17 mmol/L, respectively. The median z-score for the weight for age and height for age at initial presentation was -4.77 (-7.68 to -3.74) and -4.21 (-5.42 to -2.37) and at follow-up was -3.35 (-5.29 to -1.55) and -3.84 (-5.36 to -1.63), respectively. Twenty-two (78.6%) children had medullary nephrocalcinosis. Four children had sensorineural hearing loss. Seven children had genetic testing done, and six had pathogenic or likely pathogenic variants in ATP6V1B1 and ATP6V0A4 gene. Children with dRTA have a guarded prognosis and ATP6V1B1 and ATP6V0A4 mutations are the most common implicated genetic defect in Indian children with distal RTA.
{"title":"Phenotype and Genotype Profile of Children with Primary Distal Renal Tubular Acidosis: A 10-Year Experience from a North Indian Teaching Institute.","authors":"Lesa Dawman, Karalanglin Tiewsoh, Prabal Barman, Kambagiri Pratyusha, Lalawmpuia Chaakchhuak, Indar Kumar Sharawat","doi":"10.1055/s-0041-1724114","DOIUrl":"https://doi.org/10.1055/s-0041-1724114","url":null,"abstract":"<p><p>Primary distal renal tubular acidosis (dRTA) or Type 1 RTA in children is caused by a genetic defect (involved genes <i>ATP6V0A4</i> , <i>ATP6V1B1</i> , <i>SLC4A1</i> , <i>FOXI1</i> , or <i>WDR72</i> ), which causes tubular transport defects characterized by an inability to appropriately acidify urine with resultant persistent hyperchloremic metabolic acidosis. Retrospective analysis of 28 children (14 males) under the age of 14 years with dRTA seen from 2010 to 2019 was reviewed, and detailed clinic records were analyzed. The clinical features, investigations, and response to treatment were recorded. The median age of the children at presentation was 30 months (range: 9.25-72 months), and the median age at onset of symptoms was 2 months. All the children had growth failure, polyuria, and polydipsia at presentation. Mean serum potassium, pH, bicarbonate, and anion gap at presentation was 2.3 ± 0.5 mmol/L, 7.22 ± 0.09, 13.28 ± 4.37 mmol/L, and 9.3 ± 2.18, respectively. Mean serum potassium, pH, bicarbonate at follow-up was 3.88 ± 0.6 mmol/L, 7.35 ± 0.06, and 20.13 ± 4.17 mmol/L, respectively. The median z-score for the weight for age and height for age at initial presentation was -4.77 (-7.68 to -3.74) and -4.21 (-5.42 to -2.37) and at follow-up was -3.35 (-5.29 to -1.55) and -3.84 (-5.36 to -1.63), respectively. Twenty-two (78.6%) children had medullary nephrocalcinosis. Four children had sensorineural hearing loss. Seven children had genetic testing done, and six had pathogenic or likely pathogenic variants in <i>ATP6V1B1</i> and <i>ATP6V0A4</i> gene. Children with dRTA have a guarded prognosis and <i>ATP6V1B1</i> and <i>ATP6V0A4</i> mutations are the most common implicated genetic defect in Indian children with distal RTA.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"11 3","pages":"221-226"},"PeriodicalIF":0.4,"publicationDate":"2021-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385252/pdf/10-1055-s-0041-1724114.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40712730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01Epub Date: 2020-07-29DOI: 10.1055/s-0040-1714701
Dorota Wicher, Łukasz Obrycki, Irena Jankowska
Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common ciliopathies with kidney (nephromegaly, hypertension, renal dysfunction) and liver involvement (congenital hepatic fibrosis, dilated bile ducts). Clinical features also include growth failure and neurocognitive impairment. Plurality of clinical aspects requires multidisciplinary approach to treatment and care of patients. Until recently, diagnosis was based on clinical criteria. Results of genetic testing show the molecular basis of polycystic kidneys disease is heterogeneous, and differential diagnosis is essential. The aim of the article is to discuss the role of genetic testing and its difficulties in diagnostics of ARPKD in children.
{"title":"Autosomal Recessive Polycystic Kidney Disease-The Clinical Aspects and Diagnostic Challenges.","authors":"Dorota Wicher, Łukasz Obrycki, Irena Jankowska","doi":"10.1055/s-0040-1714701","DOIUrl":"https://doi.org/10.1055/s-0040-1714701","url":null,"abstract":"<p><p>Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common ciliopathies with kidney (nephromegaly, hypertension, renal dysfunction) and liver involvement (congenital hepatic fibrosis, dilated bile ducts). Clinical features also include growth failure and neurocognitive impairment. Plurality of clinical aspects requires multidisciplinary approach to treatment and care of patients. Until recently, diagnosis was based on clinical criteria. Results of genetic testing show the molecular basis of polycystic kidneys disease is heterogeneous, and differential diagnosis is essential. The aim of the article is to discuss the role of genetic testing and its difficulties in diagnostics of ARPKD in children.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 1","pages":"1-8"},"PeriodicalIF":0.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0040-1714701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 ( NUDT15 ) genes have been proposed as key determinants of 6-mercaptopurine (6-MP)-induced myelosuppression in pediatric acute lymphoblastic leukemia (ALL). In the present study, genotypes of TPMT and NUDT15 were investigated in 178 Thai pediatric patients with ALL by the TaqMan SNP genotyping assay and DNA sequencing. The frequency of TPMT*3C was 0.034. Among NUDT15 variants, NUDT15*3 is the most common variant with the allele frequency of 0.073, whereas those of NUDT15*2 , NUDT15*5 , and NUDT15*6 variants were 0.022, 0.011, and 0.039. These data suggest that a high proportion of Thai pediatric ALL patients may be at risk of thiopurine-induced myelosuppression.
{"title":"Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients.","authors":"Kanyarat Khaeso, Nontaya Nakkam, Patcharee Komwilaisak, Piyathida Wongmast, Su-On Chainansamit, Areerat Dornsena, Sirimas Kanjanawart, Suda Vannaprasaht, Wichittra Tassaneeyakul","doi":"10.1055/s-0040-1715818","DOIUrl":"https://doi.org/10.1055/s-0040-1715818","url":null,"abstract":"<p><p>Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 ( <i>NUDT15</i> ) genes have been proposed as key determinants of 6-mercaptopurine (6-MP)-induced myelosuppression in pediatric acute lymphoblastic leukemia (ALL). In the present study, genotypes of <i>TPMT</i> and <i>NUDT15</i> were investigated in 178 Thai pediatric patients with ALL by the TaqMan SNP genotyping assay and DNA sequencing. The frequency of <i>TPMT*3C</i> was 0.034. Among <i>NUDT15</i> variants, <i>NUDT15*3</i> is the most common variant with the allele frequency of 0.073, whereas those of <i>NUDT15*2</i> , <i>NUDT15*5</i> , and <i>NUDT15*6</i> variants were 0.022, 0.011, and 0.039. These data suggest that a high proportion of Thai pediatric ALL patients may be at risk of thiopurine-induced myelosuppression.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 1","pages":"29-34"},"PeriodicalIF":0.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0040-1715818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01Epub Date: 2020-02-12DOI: 10.1055/s-0040-1701640
Bruna Lixinski Diniz, Andressa Barreto Glaeser, Desirée Deconte, Bruna Baierle Guaraná, Rafael Fabiano Machado Rosa, Paulo Ricardo Gazzola Zen
Ectopic calcification in soft tissue is associated with several disorders including pseudohypoparathyroidism (PHP), which is characterized by resistance or nonresponse to parathyroid hormone (PTH) function. Association between PHP and 22q11DS, also known as DiGeorge syndrome, is rare, especially in children. We describe a newborn girl diagnosed with 22q11DS, presenting ectopic calcifications in soft tissue and suspicion of PHP. PTH function showed values close to the upper limit of the reference value. Radiology showed bone callus in the right wrist. PHP can be a new clinical finding associated with 22q11DS. Parathyroid function investigation in individuals with 22q11DS, presenting bone dysmorphisms and/or calcium metabolism alterations, should be considered.
{"title":"Pseudohypoparathyroidism with Ectopic Calcification and 22q11 Deletion Syndrome: A Rare Case.","authors":"Bruna Lixinski Diniz, Andressa Barreto Glaeser, Desirée Deconte, Bruna Baierle Guaraná, Rafael Fabiano Machado Rosa, Paulo Ricardo Gazzola Zen","doi":"10.1055/s-0040-1701640","DOIUrl":"https://doi.org/10.1055/s-0040-1701640","url":null,"abstract":"<p><p>Ectopic calcification in soft tissue is associated with several disorders including pseudohypoparathyroidism (PHP), which is characterized by resistance or nonresponse to parathyroid hormone (PTH) function. Association between PHP and 22q11DS, also known as DiGeorge syndrome, is rare, especially in children. We describe a newborn girl diagnosed with 22q11DS, presenting ectopic calcifications in soft tissue and suspicion of PHP. PTH function showed values close to the upper limit of the reference value. Radiology showed bone callus in the right wrist. PHP can be a new clinical finding associated with 22q11DS. Parathyroid function investigation in individuals with 22q11DS, presenting bone dysmorphisms and/or calcium metabolism alterations, should be considered.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 1","pages":"45-48"},"PeriodicalIF":0.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0040-1701640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Multiplex ligation-dependent probe amplification (MLPA) detects exonic deletions and duplications in the DMD gene in around 65 to 70% of patients with the Duchenne muscular dystrophy (DMD) phenotype. This study looks at the diagnostic yield of next-generation sequencing (NGS) and the mutation spectrum in an Asian Indian cohort of MLPA-negative cases with the DMD phenotype. NGS-based sequencing of DMD gene was done in 28 MLPA-negative cases (25 male probands with the DMD phenotype and 3 obligate carrier mothers of deceased affected male patients) and disease-causing variants were identified in 19 (67.9%) of these cases. Further molecular testing in four of the remaining nine cases revealed gene variants associated with limb girdle muscular dystrophies. Thus, NGS-based multigene panel testing for muscular dystrophy-associated genes or clinical exome sequencing rather than targeted DMD gene sequencing appears to be a more cost-effective testing modality with better diagnostic yield, for MLPA-negative patients with the DMD phenotype.
{"title":"Next-Generation Sequencing in a Cohort of Asian Indian Patients with the Duchenne Muscular Dystrophy Phenotype: Diagnostic Yield and Mutation Spectrum.","authors":"Gayatri Nerakh, Prajnya Ranganath, Sakthivel Murugan","doi":"10.1055/s-0040-1713850","DOIUrl":"https://doi.org/10.1055/s-0040-1713850","url":null,"abstract":"<p><p>Multiplex ligation-dependent probe amplification (MLPA) detects exonic deletions and duplications in the <i>DMD</i> gene in around 65 to 70% of patients with the Duchenne muscular dystrophy (DMD) phenotype. This study looks at the diagnostic yield of next-generation sequencing (NGS) and the mutation spectrum in an Asian Indian cohort of MLPA-negative cases with the DMD phenotype. NGS-based sequencing of <i>DMD</i> gene was done in 28 MLPA-negative cases (25 male probands with the DMD phenotype and 3 obligate carrier mothers of deceased affected male patients) and disease-causing variants were identified in 19 (67.9%) of these cases. Further molecular testing in four of the remaining nine cases revealed gene variants associated with limb girdle muscular dystrophies. Thus, NGS-based multigene panel testing for muscular dystrophy-associated genes or clinical exome sequencing rather than targeted <i>DMD</i> gene sequencing appears to be a more cost-effective testing modality with better diagnostic yield, for MLPA-negative patients with the DMD phenotype.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 1","pages":"23-28"},"PeriodicalIF":0.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0040-1713850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The deletion of the long arm of chromosome 4 is rare, presenting with a variable phenotype depending on the chromosomic area affected. A term newborn with prenatal diagnosis of anhydramnios, dysplastic cystic kidneys, and cardiomegaly was born with generalized subcutaneous edema, several dysmorphic features, and progressive renal failure requiring dialysis. The infant continued to deteriorate and died at 52 days of age. Autopsy confirmed bilateral renal dysplasia with cysts. Array-comparative genomic hybridization (CGH) identified a large deletion on 4q25-q28.3, which is not yet described in association with renal disease. The clinical progression could be expected due to the severity of the perinatal clinical presentation.
{"title":"Renal Dysplasia and Progressive Renal Failure in a Newborn with Interstitial Chromosome 4 Deletion 4q25-28.3: A New Phenotype?","authors":"Cláudia Teles-Silva, Francisca Martins, Sandra Costa, Paulo Soares, Gustavo Rocha, Filipa Flor-de-Lima, Helena Pinto, Carla Ramalho, Renata Oliveira, Otília Brandão, Hercília Guimarães","doi":"10.1055/s-0039-1701043","DOIUrl":"https://doi.org/10.1055/s-0039-1701043","url":null,"abstract":"<p><p>The deletion of the long arm of chromosome 4 is rare, presenting with a variable phenotype depending on the chromosomic area affected. A term newborn with prenatal diagnosis of anhydramnios, dysplastic cystic kidneys, and cardiomegaly was born with generalized subcutaneous edema, several dysmorphic features, and progressive renal failure requiring dialysis. The infant continued to deteriorate and died at 52 days of age. Autopsy confirmed bilateral renal dysplasia with cysts. Array-comparative genomic hybridization (CGH) identified a large deletion on 4q25-q28.3, which is not yet described in association with renal disease. The clinical progression could be expected due to the severity of the perinatal clinical presentation.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 1","pages":"39-44"},"PeriodicalIF":0.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0039-1701043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Complete labyrinthine aplasia (CLA) is a rare inner ear anomaly. The only identified genetic cause of CLA with severe sensorineural hearing loss is labyrinthine aplasia, microtia, and microdontia (LAMM) syndrome. Here we reported a child who presented with syndromic hearing loss and was diagnosed with LAMM syndrome. Genetic evaluation provided the family with confirmation of the diagnosis, provision of the prognosis, genetic counselling, and prenatal diagnosis. This report highlighted that CLA should be recognized as a unique sign to diagnose LAMM syndrome, to analyze FGF3 gene mutation, and also demonstrated the utility of genetic testing in patients with suspected LAMM syndrome to provide exact diagnosis and further management.
{"title":"Complete Labyrinthine Aplasia: A Unique Sign for Targeted Genetic Testing in Hearing Loss.","authors":"Meenakshi Lallar, Veronica Arora, Renu Saxena, Ratna Dua Puri, Ishwar Chander Verma","doi":"10.1055/s-0040-1708052","DOIUrl":"https://doi.org/10.1055/s-0040-1708052","url":null,"abstract":"<p><p>Complete labyrinthine aplasia (CLA) is a rare inner ear anomaly. The only identified genetic cause of CLA with severe sensorineural hearing loss is labyrinthine aplasia, microtia, and microdontia (LAMM) syndrome. Here we reported a child who presented with syndromic hearing loss and was diagnosed with LAMM syndrome. Genetic evaluation provided the family with confirmation of the diagnosis, provision of the prognosis, genetic counselling, and prenatal diagnosis. This report highlighted that CLA should be recognized as a unique sign to diagnose LAMM syndrome, to analyze <i>FGF3</i> gene mutation, and also demonstrated the utility of genetic testing in patients with suspected LAMM syndrome to provide exact diagnosis and further management.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 1","pages":"70-73"},"PeriodicalIF":0.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0040-1708052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01Epub Date: 2020-01-20DOI: 10.1055/s-0039-1701020
Jason L Williams, Marie T McDonald, Bryce A Seifert, Kristen L Deak, Catherine W Rehder, Michael J Campbell
Cat eye syndrome (CES) is a rare genetic defect, characterized by iris colobomas, preauricular skin tags, and anal malformations. Affecting 1 in 150,000 people, this defect is caused by duplication or triplication of the proximal long (q) arm of chromosome 22. Congenital heart disease is associated with CES. One of the most common heart defects in patients with CES is total anomalous pulmonary venous return (TAPVR). In this article, we reported patients with a rare association of concomitant TAPVR and aortic arch obstruction: one with interrupted aortic arch and the other with coarctation of the aorta with an aberrant right subclavian artery.
{"title":"An Unusual Association: Total Anomalous Pulmonary Venous Return and Aortic Arch Obstruction in Patients with Cat Eye Syndrome.","authors":"Jason L Williams, Marie T McDonald, Bryce A Seifert, Kristen L Deak, Catherine W Rehder, Michael J Campbell","doi":"10.1055/s-0039-1701020","DOIUrl":"10.1055/s-0039-1701020","url":null,"abstract":"<p><p>Cat eye syndrome (CES) is a rare genetic defect, characterized by iris colobomas, preauricular skin tags, and anal malformations. Affecting 1 in 150,000 people, this defect is caused by duplication or triplication of the proximal long (q) arm of chromosome 22. Congenital heart disease is associated with CES. One of the most common heart defects in patients with CES is total anomalous pulmonary venous return (TAPVR). In this article, we reported patients with a rare association of concomitant TAPVR and aortic arch obstruction: one with interrupted aortic arch and the other with coarctation of the aorta with an aberrant right subclavian artery.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 1","pages":"35-38"},"PeriodicalIF":0.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0039-1701020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01Epub Date: 2020-04-25DOI: 10.1055/s-0040-1710330
Fady P Marji, Jennifer A Hall, Erin Anstadt, Suneeta Madan-Khetarpal, Jesse A Goldstein, Joseph E Losee
De novo heterozygous mutations in the KAT6A gene give rise to a distinct intellectual disability syndrome, with features including speech delay, cardiac anomalies, craniofacial dysmorphisms, and craniosynostosis. Here, we reported a 16-year-old girl with a novel pathogenic variant of the KAT6A gene. She is the first case to possess pancraniosynostosis, a rare suture fusion pattern, affecting all her major cranial sutures. The diagnosis of KAT6A syndrome is established via recognition of its inherent phenotypic features and the utilization of whole exome sequencing. Thorough craniofacial evaluation is imperative, craniosynostosis may require operative intervention, the delay of which may be detrimental.
{"title":"A Novel Frameshift Mutation in KAT6A Is Associated with Pancraniosynostosis.","authors":"Fady P Marji, Jennifer A Hall, Erin Anstadt, Suneeta Madan-Khetarpal, Jesse A Goldstein, Joseph E Losee","doi":"10.1055/s-0040-1710330","DOIUrl":"https://doi.org/10.1055/s-0040-1710330","url":null,"abstract":"<p><p>De novo heterozygous mutations in the <i>KAT6A</i> gene give rise to a distinct intellectual disability syndrome, with features including speech delay, cardiac anomalies, craniofacial dysmorphisms, and craniosynostosis. Here, we reported a 16-year-old girl with a novel pathogenic variant of the <i>KAT6A</i> gene. She is the first case to possess pancraniosynostosis, a rare suture fusion pattern, affecting all her major cranial sutures. The diagnosis of KAT6A syndrome is established via recognition of its inherent phenotypic features and the utilization of whole exome sequencing. Thorough craniofacial evaluation is imperative, craniosynostosis may require operative intervention, the delay of which may be detrimental.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 1","pages":"81-84"},"PeriodicalIF":0.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0040-1710330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01Epub Date: 2020-06-10DOI: 10.1055/s-0040-1713154
Nihal Inandiklioğlu, Adem Yaşar
Several studies have shown that rs9939609 and rs1421085 in fat mass and obesity-associated ( FTO ) gene rs17782313 and rs12970134 in melanocortin-4 receptor ( MC4R ) gene influence obesity. In the present study, we aimed to determine association between rs9939609, rs1421085, rs17782313, and rs12970134 polymorphism, and their relation with body mass index (BMI), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and lipid values in obese children. We included 100 newly diagnosed obese children and 100 healthy children. The rs1421085 (CC/CT) ( p = 0.019) and rs9939609 (AA/AT) ( p = 0.002) polymorphism regions were higher in the obese group. Additionally, we found that both the rs1421085 (CC/CT) and rs9939609 (AA/AT) polymorphism associated with high-density lipoprotein cholesterol ( p = 0.011 and p = 0.003) and triglycerides ( p = 0.01 and p = 0.004) level, respectively. Further, the rs9939609 and rs1421085 variants of FTO gene associated with HDL-cholesterol and triglycerides levels in obese children; however, updated studies with a large sample size are required to establish strong links with genetic variants and risk factors in childhood obesity.
{"title":"Association between rs1421085 and rs9939609 Polymorphisms of Fat Mass and Obesity-Associated Gene with High-Density Lipoprotein Cholesterol and Triglyceride in Obese Turkish Children and Adolescents.","authors":"Nihal Inandiklioğlu, Adem Yaşar","doi":"10.1055/s-0040-1713154","DOIUrl":"https://doi.org/10.1055/s-0040-1713154","url":null,"abstract":"<p><p>Several studies have shown that rs9939609 and rs1421085 in fat mass and obesity-associated ( <i>FTO</i> ) gene rs17782313 and rs12970134 in melanocortin-4 receptor ( <i>MC4R</i> ) gene influence obesity. In the present study, we aimed to determine association between rs9939609, rs1421085, rs17782313, and rs12970134 polymorphism, and their relation with body mass index (BMI), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and lipid values in obese children. We included 100 newly diagnosed obese children and 100 healthy children. The rs1421085 (CC/CT) ( <i>p</i> = 0.019) and rs9939609 (AA/AT) ( <i>p</i> = 0.002) polymorphism regions were higher in the obese group. Additionally, we found that both the rs1421085 (CC/CT) and rs9939609 (AA/AT) polymorphism associated with high-density lipoprotein cholesterol ( <i>p</i> = 0.011 and <i>p</i> = 0.003) and triglycerides ( <i>p</i> = 0.01 and <i>p</i> = 0.004) level, respectively. Further, the rs9939609 and rs1421085 variants of <i>FTO</i> gene associated with HDL-cholesterol and triglycerides levels in obese children; however, updated studies with a large sample size are required to establish strong links with genetic variants and risk factors in childhood obesity.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 1","pages":"9-15"},"PeriodicalIF":0.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0040-1713154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}