Journal of pediatric genetics最新文献_第2页

X-Linked Myotubular Myopathy: A Novel Mutation Expanding the Genotypic Spectrum of a Phenotypically Heterogeneous Myopathy. x连锁肌小管肌病:一种扩大表型异质性肌病基因型谱的新突变。

IF 0.4

Journal of pediatric genetics Pub Date : 2023-09-01 DOI: 10.1055/s-0041-1728745

Andreia Carvalho, Carmen Costa, Miguel Pinto, Ricardo Taipa, Ana Gonçalves, Márcia E Oliveira, Sofia Ferreira, Joana Afonso Ribeiro

{"title":"X-Linked Myotubular Myopathy: A Novel Mutation Expanding the Genotypic Spectrum of a Phenotypically Heterogeneous Myopathy.","authors":"Andreia Carvalho, Carmen Costa, Miguel Pinto, Ricardo Taipa, Ana Gonçalves, Márcia E Oliveira, Sofia Ferreira, Joana Afonso Ribeiro","doi":"10.1055/s-0041-1728745","DOIUrl":"https://doi.org/10.1055/s-0041-1728745","url":null,"abstract":"X-linked myotubular myopathy (XLMTM), a centronuclear congenital myopathy secondary to pathogenic variants in the MTM1 gene encoding myotubularin, is typically recognized for its classic and severe phenotype which includes neonatal hypotonia, severe muscle weakness, long-term ventilator dependence, markedly delayed gross motor milestones with inability to independently ambulate, and a high neonatal and childhood mortality. However, milder congenital forms of the condition and other phenotypes are recognized. We describe a 6-year-old boy with a mild XLMTM phenotype with independent gait and no respiratory insufficiency even in the neonatal period. The child has a hemizygous novel splice site variant in the MTM1 gene (c.232-25A > T) whose pathogenicity was confirmed by cDNA studies (exon 5 skipping) and muscle biopsy findings. We also compared the phenotype of our patient with the few reported cases that presented a mild XLMTM phenotype and no respiratory distress at birth, and discussed the potential mechanisms underlying this phenotype such as the presence of residual expression of the normal myotubularin transcript.","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 3","pages":"258-262"},"PeriodicalIF":0.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421687/pdf/10-1055-s-0041-1728745.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9998200","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}

引用次数: 0

The Efficacy of Whole Genome Sequencing and RNA-Seq in the Diagnosis of Whole Exome Sequencing Negative Patients with Complex Neurological Phenotypes. 全基因组测序和RNA-Seq在复杂神经表型全外显子组测序阴性患者诊断中的作用

IF 0.4

Journal of pediatric genetics Pub Date : 2023-09-01 DOI: 10.1055/s-0041-1736610

Bianca Blake, Lauren I Brady, Nicholas A Rouse, Peter Nagy, Mark A Tarnopolsky

{"title":"The Efficacy of Whole Genome Sequencing and RNA-Seq in the Diagnosis of Whole Exome Sequencing Negative Patients with Complex Neurological Phenotypes.","authors":"Bianca Blake, Lauren I Brady, Nicholas A Rouse, Peter Nagy, Mark A Tarnopolsky","doi":"10.1055/s-0041-1736610","DOIUrl":"https://doi.org/10.1055/s-0041-1736610","url":null,"abstract":"Whole-genome sequencing (WGS) is being increasingly utilized for the diagnosis of neurological disease by sequencing both the exome and the remaining 98 to 99% of the genetic code. In addition to more complete coverage, WGS can detect structural variants (SVs) and intronic variants (SNVs) that cannot be identified by whole exome sequencing (WES) or chromosome microarray (CMA). Other multi-omics tools, such as RNA sequencing (RNA-Seq), can be used in conjunction with WGS to functionally validate certain variants by detecting changes in gene expression and splicing. The objective of this retrospective study was to measure the diagnostic yield of duo/trio-based WGS and RNA-Seq in a cohort of 22 patients (20 families) with pediatric onset neurological phenotypes and negative or inconclusive WES results in lieu of reanalysis. WGS with RNA-Seq resulted in a definite diagnosis of an additional 25% of cases. Sixty percent of these solved cases arose from the identification of variants that were missed by WES. Variants that could not be unequivocally proven to be causative of the patients' condition were identified in an additional 5% of cases.","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 3","pages":"206-212"},"PeriodicalIF":0.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421693/pdf/10-1055-s-0041-1736610.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10370953","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}

引用次数: 0

Case Series of Ethylmalonic Encephalopathy from Southern India. 印度南部乙基丙二酸脑病病例系列。

IF 0.4

Journal of pediatric genetics Pub Date : 2023-09-01 DOI: 10.1055/s-0041-1740370

Vykuntaraju K Gowda, Varunvenkat M Srinivasan, Kapil Jetha, Kiruthiga Sugumar, Meenakshi Bhat, Sanjay K Shivappa, Maya Bhat, Rita Christopher

{"title":"Case Series of Ethylmalonic Encephalopathy from Southern India.","authors":"Vykuntaraju K Gowda, Varunvenkat M Srinivasan, Kapil Jetha, Kiruthiga Sugumar, Meenakshi Bhat, Sanjay K Shivappa, Maya Bhat, Rita Christopher","doi":"10.1055/s-0041-1740370","DOIUrl":"https://doi.org/10.1055/s-0041-1740370","url":null,"abstract":"Ethylmalonic encephalopathy is a rare neurometabolic disorder with central nervous system involvement and vasculopathy. It is presented in infancy with developmental delay, acrocyanosis, petechiae, chronic diarrhea, and early death. This was a retrospective study of confirmed cases of ethylmalonic aciduria from a tertiary care hospital over a period of 5 years from January 2015 to December 2020. Case details including analysis of clinical history, investigations, and outcomes are presented. Of six cases, male-to-female ratio was 4:2. Mean age of presentation was 35.5 months (range: 14-83 months). Consanguinity, global developmental delay, failure to thrive, skin rashes, microcephaly, hypotonia, and exaggerated deep tendon reflexes were observed in all cases. Chronic diarrhea was presented in five cases. The serum levels of C4 carnitine and urinary levels of ethylmalonic acid were increased in all cases. Magnetic resonance imaging (MRI) of the brain showed heterogenous bilateral symmetrical changes in the basal ganglia in five cases, and in one case, MRI could not be done. Genetic testing in two cases showed a homozygous variant in ETHE1 gene. Four children died, while the other two cases showed a decreased in recurrent encephalopathies and diarrhea after starting metronidazole. All children had global developmental delay, failure to thrive, skin rashes, central hypotonia, increased C4 carnitine levels in the serum, and increased ethylmalonic acid in the urine. Chronic diarrhea, acrocyanosis, and basal ganglia change in the MRI of the brain also give important clues for diagnosis. Metronidazole is useful in preventing recurrent episodes of encephalopathy.","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 3","pages":"213-218"},"PeriodicalIF":0.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421674/pdf/10-1055-s-0041-1740370.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9995776","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}

引用次数: 0

Electroclinical Improvement in a Patient with Ring Chromosome 20 Syndrome Treated with Zonisamide: A Case Report. 唑尼沙胺治疗20环染色体综合征1例电临床改善。

IF 0.4

Journal of pediatric genetics Pub Date : 2023-09-01 DOI: 10.1055/s-0041-1726281

Stefano Parravicini, Ludovica Pasca, Martina Paola Zanaboni, Costanza Varesio, Elisa Rognone, Martina Totaro, Simone Gana, Elena Rossi, Valentina De Giorgis

引用次数: 0

Novel Radiological Brain Anomalies in a Patient with Congenital Muscular Dystrophy due to FKRP Mexican Founder Mutation c.1387A > G: Review of the Literature. FKRP墨西哥方正突变c.1387A > G引起的先天性肌营养不良患者的新型放射学脑异常:文献综述。

IF 0.4

Journal of pediatric genetics Pub Date : 2023-09-01 DOI: 10.1055/s-0041-1726470

Marivi Cervera-Gaviria, Julia Enterría-Rosales, Juan José Juárez-Vignon-Whaley, Julián García-Sánchez, Rodrigo Treviño-Velasco, Jaime Cervera-Gaviria

{"title":"Novel Radiological Brain Anomalies in a Patient with Congenital Muscular Dystrophy due to FKRP Mexican Founder Mutation c.1387A > G: Review of the Literature.","authors":"Marivi Cervera-Gaviria, Julia Enterría-Rosales, Juan José Juárez-Vignon-Whaley, Julián García-Sánchez, Rodrigo Treviño-Velasco, Jaime Cervera-Gaviria","doi":"10.1055/s-0041-1726470","DOIUrl":"https://doi.org/10.1055/s-0041-1726470","url":null,"abstract":"Mutations in the FKRP gene result in phenotypes with severe forms of congenital muscular dystrophies (CMD) and limb-girdle muscular dystrophies. We present a Mexican patient with a pathogenic homozygous mutation in the FKRP gene (c.1387A > G, p.Asn463Asp) and CMD with radiological brain anomalies as disseminated hyperintensity lesions and discrete generalized cortical atrophy. These findings have not been reported to the best of our knowledge in other patients with the same mutation. The mutation c.1387A > G, p.Asn463Asp in the FKRP gene has been described to have a founder effect in central Mexico, since all the patients described to date are of Hispanic origin. Therefore, we emphasize studying mutations in the FKRP gene in Hispanic pediatric patients with clinical suspicion of CMD. Clinical and molecular diagnosis of specific CMD subtypes is needed to help clarify the prognosis, management, and genetic counseling to the patient and families.","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 3","pages":"237-241"},"PeriodicalIF":0.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421689/pdf/10-1055-s-0041-1726470.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9995777","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}

引用次数: 0

A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome. 一种新的MN1基因致病变异在一名表现为菱脑突触和颅面异常的患者中，扩大了MN1 c端截断综合征。

IF 0.4

Journal of pediatric genetics Pub Date : 2023-09-01 DOI: 10.1055/s-0041-1728650

Carmen Palma Milla, Pérez Mohand Patricia, José M Lezana, Jaime Cruz, Juan F Quesada, Sara Vila, Isabel Álvarez-Mora, Ana Arteche-López, Irene Gómez-Manjón, M Teresa Sánchez, Maria José Gómez-Rodríguez, Jaime Sánchez, Marta Moreno-García

{"title":"A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome.","authors":"Carmen Palma Milla, Pérez Mohand Patricia, José M Lezana, Jaime Cruz, Juan F Quesada, Sara Vila, Isabel Álvarez-Mora, Ana Arteche-López, Irene Gómez-Manjón, M Teresa Sánchez, Maria José Gómez-Rodríguez, Jaime Sánchez, Marta Moreno-García","doi":"10.1055/s-0041-1728650","DOIUrl":"https://doi.org/10.1055/s-0041-1728650","url":null,"abstract":"Meningioma-1 is a transcription activator that regulates mammalian palate development and is required for appropriate osteoblast proliferation, motility, differentiation, and function. Microdeletions involving the MN1 gene have been linked to syndromes including craniofacial anomalies, such as Toriello-Carey syndrome. Recently, truncating variants in the C-terminal portion of the MN1 transcriptional factor have been linked to a characteristic and distinct phenotype presenting with craniofacial anomalies and partial rhombencephalosynapsis, a rare brain malformation characterized by midline fusion of the cerebellar hemispheres with partial or complete loss of the cerebellar vermis. It has been called MN1 C-terminal truncation (MCTT) syndrome or CEBALID (Craniofacial defects, dysmorphic Ears, Brain Abnormalities, Language delay, and Intellectual Disability) and suggested to be caused by dominantly acting truncated protein MN1 instead of haploinsufficiency. As a proto-oncogene, MN1 is also involved in familial meningioma. In this study, we present a novel case of MCTT syndrome in a female patient presenting with craniofacial anomalies and rhombencephalosynapsis, harboring a de novo pathogenic variant in the MN1 gene: c.3686_3698del, p.(Met1229Argfs*87).","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 3","pages":"254-257"},"PeriodicalIF":0.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421676/pdf/10-1055-s-0041-1728650.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10370951","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}

引用次数: 0

Neu-Laxova's Syndrome: A Case Report of a Fetus with Novel Mutation in PHGDH Gene and a Literature Review. 新拉索瓦综合征:胎儿PHGDH基因突变1例并文献复习。

IF 0.4

Journal of pediatric genetics Pub Date : 2023-09-01 DOI: 10.1055/s-0041-1726038

Ravi Kapoor, Seema Thakur, Aakar Kapoor, Sunita Kapoor, Apurva Kalra, Aakriti Kapoor

引用次数: 0

Deficiency of Interleukin-1 Receptor Antagonist: New Genetic Autoinflammatory Disease as a Diagnostic Challenge for Pediatricians. 白细胞介素-1受体拮抗剂缺乏:新的遗传性自身炎症疾病作为儿科医生的诊断挑战。

IF 0.4

Journal of pediatric genetics Pub Date : 2023-09-01 DOI: 10.1055/s-0041-1724113

Andrea Rivera-Sepulveda, Francisco Colón-Fontánez, Maricarmen López, Gilberto Puig-Ramos

{"title":"Deficiency of Interleukin-1 Receptor Antagonist: New Genetic Autoinflammatory Disease as a Diagnostic Challenge for Pediatricians.","authors":"Andrea Rivera-Sepulveda, Francisco Colón-Fontánez, Maricarmen López, Gilberto Puig-Ramos","doi":"10.1055/s-0041-1724113","DOIUrl":"https://doi.org/10.1055/s-0041-1724113","url":null,"abstract":"Deficiency of interleukin-1 receptor antagonist is a rare autoinflammatory disease that affects infants early in life. It often presents with systemic inflammation, skin and bone involvement. We present a 5-month-old boy who was hospitalized due to generalized erythematous pustular eruption with secondary impetigo, cellulitis, bronchiolitis, and elevated inflammatory markers. The patient was unresponsive to multiple courses of intravenous antibiotics, systemic, and topical steroid medications. The patient was evaluated by dermatology and rheumatology services among other subspecialities. Skin biopsy showed changes consistent with psoriasiform dermatitis, while bone scans showed multifocal osteomyelitis. The patient was started empirically on anakinra with improvement at 72 hours upon administration. This is one of the youngest reported case in the literature to be started on anakinra empirically prior to genetic confirmation of the mutation. A comprehensive literature review revealed that approximately 20 genetically confirmed patients, including our patient, have been reported with this genetic disease. It is imperative to recognize this disease early to achieve adequate response and remission. Therefore, clinical symptoms and the associated differential diagnosis for this disease should be constantly reassessed and reviewed by pediatricians and subspecialists to detect the disease as early as possible and reduce the high morbidity and mortality associated with delayed diagnosis and treatment.","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 3","pages":"227-232"},"PeriodicalIF":0.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421680/pdf/10-1055-s-0041-1724113.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9989405","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}

引用次数: 0

Esophageal Stricture and Dermal Pathology Related to Compound Heterozygous Mutations in the TNXB Gene. 与TNXB基因复合杂合突变相关的食管狭窄和皮肤病理。

IF 0.4

Journal of pediatric genetics Pub Date : 2023-09-01 DOI: 10.1055/s-0041-1724048

Nida Mirza, Sundeep Upadhyaya, Sagar Mehta, Smita Malhotra, Anupam Sibal

引用次数: 0

Genesis of a Fact: Tay-Sachs Disease as a "Simple Recessive". 事实的起源：泰-萨克斯病是一种 "简单隐性遗传病"。

IF 0.4

Journal of pediatric genetics Pub Date : 2023-06-12 eCollection Date: 2023-09-01 DOI: 10.1055/s-0043-1769115

Mark Lubinsky

{"title":"Genesis of a Fact: Tay-Sachs Disease as a \"Simple Recessive\".","authors":"Mark Lubinsky","doi":"10.1055/s-0043-1769115","DOIUrl":"10.1055/s-0043-1769115","url":null,"abstract":"\"Obvious\" recessive inheritance of Tay-Sachs disease (TSD; OMIM # 272800) took over half a century to be established. Points now taken for granted were problematic, that: (1) TSD is a biological entity, not an artificial selection of concurrent findings, (2) manifestations have narrow limits, (3) it was not part of a spectrum of disorders, and can be differentiated from other conditions, (4) it will not change to another disease, (5) it is due to a single specific gene, (6) there are no secondary causes, (7) the gene has no apparent clinical effects unrelated to TSD, and (8) the gene is inherited only as a clinical recessive. To a large extent, resolution reflected biochemical understanding that took until mid-20th century, and beyond, to change how physicians viewed diseases in general. With this, biochemical carrier screening and prenatal biochemical diagnosis have become routinely available, and it is a model for carrier population screening, while gene therapy for the disease has been reported with some degree of success. Here, the history of medical ideas about TSD and its inheritance are reviewed to show how it achieved its current status as a distinct recessive disorder.","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 3","pages":"187-192"},"PeriodicalIF":0.4,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9989409","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}

引用次数: 0