Somatic and germline analysis of a familial Rothmund–Thomson syndrome in two siblings with osteosarcoma

AbstractRothmund–Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted.

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Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report

BMC Musculoskeletal Disorders ◽

10.1186/s12891-020-03890-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Samina Yasin ◽

Outi Makitie ◽

Sadaf Naz

Keyword(s):

Short Stature ◽

Autosomal Recessive ◽

Autosomal Recessive Disorder ◽

Loss Of Function ◽

Case Presentation ◽

Pathogenic Variants ◽

Skeletal Malformations ◽

Tarsal Bones ◽

The Family ◽

Heterozygous Carriers

Abstract Background Loss of function or gain of function variants of Filamin B (FLNB) cause recessive or dominant skeletal disorders respectively. Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive disorder characterized by short stature, fused vertebrae and fusion of carpal and tarsal bones. We present a novel FLNB homozygous pathogenic variant and present a carrier of the variant with short height. Case presentation We describe a family with five patients affected with skeletal malformations, short stature and vertebral deformities. Exome sequencing revealed a novel homozygous frameshift variant c.2911dupG p.(Ala971GlyfsTer122) in FLNB, segregating with the phenotype in the family. The variant was absent in public databases and 100 ethnically matched control chromosomes. One of the heterozygous carriers of the variant had short stature. Conclusion Our report expands the genetic spectrum of FLNB pathogenic variants. It also indicates a need to assess the heights of other carriers of FLNB recessive variants to explore a possible role in idiopathic short stature.

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Thiamine Treatment and Favorable Outcome in an Infant with Biallelic TPK1 Variants

Neuropediatrics ◽

10.1055/s-0040-1715631 ◽

2020 ◽

Author(s):

Matthias Eckenweiler ◽

Johannes A. Mayr ◽

Sarah Grünert ◽

Angela Abicht ◽

Rudolf Korinthenberg

Keyword(s):

Early Childhood ◽

Early Diagnosis ◽

Metabolic Disorder ◽

Autosomal Recessive ◽

Psychomotor Development ◽

Compound Heterozygosity ◽

Pathogenic Variants ◽

Clinical Stabilization ◽

Biotin Supplementation ◽

Thiamine Treatment

AbstractEpisodic encephalopathy due to mutations in the thiamine pyrophosphokinase 1 (TPK1) gene is a rare autosomal recessive metabolic disorder. Patients reported so far have onset in early childhood of acute encephalopathic episodes, which result in a progressive neurologic dysfunction including ataxia, dystonia, and spasticity. Here, we report the case of an infant with TPK1 deficiency (compound heterozygosity for two previously described pathogenic variants) presenting with two encephalopathic episodes and clinical stabilization under oral thiamine and biotin supplementation. In contrast to other reported cases, our patient showed an almost normal psychomotor development, which might be due to an early diagnosis and subsequent therapy.

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Prenatal and early diagnosis of Chinese 3-M syndrome patients with novel pathogenic variants

Clinica Chimica Acta ◽

10.1016/j.cca.2017.09.022 ◽

2017 ◽

Vol 474 ◽

pp. 159-164 ◽

Cited By ~ 2

Author(s):

Xuyun Hu ◽

Hongdou Li ◽

Baoheng Gui ◽

Yufei Xu ◽

Jin Wang ◽

...

Keyword(s):

Early Diagnosis ◽

Pathogenic Variants

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Dialysis Encephalopathy: A Review

The International Journal of Psychiatry in Medicine ◽

10.2190/c36r-6wgp-lcyu-9vrg ◽

1984 ◽

Vol 13 (4) ◽

pp. 309-326 ◽

Cited By ~ 23

Author(s):

Robert Jack ◽

Pauline L. Rabin ◽

T. Dwight McKinney

Keyword(s):

Differential Diagnosis ◽

Early Diagnosis ◽

Case Studies ◽

Health Personnel ◽

Diagnosis And Treatment ◽

Dialysis Encephalopathy ◽

The Family ◽

Prevention And Treatment ◽

Salient Features

Dialysis encephalopathy (DE) is a distinct neuropsychiatric syndrome typically occurring in patients undergoing longterm hemodialysis. It is characterized by electroencephalographic abnormalities in association with disturbances of speech, cognition, movement, affect, or behavior. Previously thought to be relentlessly progressive, recent evidence linking the illness to aluminum overload has led to advances in prevention and treatment. Early diagnosis aids in the reversal or amelioration of the syndrome and can be of immense value to the patient, the family and involved health personnel. The general features of the syndrome, etiologic considerations, differential diagnosis and treatment are discussed. Three case studies are included to illustrate salient features of the syndrome.

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Draft Genome Sequence of Mesosutterella multiformis JCM 32464T, a Member of the Family Sutterellaceae, Isolated from Human Feces

Microbiology Resource Announcements ◽

10.1128/mra.00478-19 ◽

2019 ◽

Vol 8 (24) ◽

Author(s):

Nao Ikeyama ◽

Moriya Ohkuma ◽

Mitsuo Sakamoto

Keyword(s):

Genome Sequence ◽

Genome Assembly ◽

Draft Genome ◽

Genomic Analysis ◽

Draft Genome Sequence ◽

Human Feces ◽

The Family ◽

Metabolic Activities

Here, we report the draft genome sequence of Mesosutterella multiformis JCM 32464T, a new member of the family Sutterellaceae that was isolated from human feces. The genome assembly comprised 2,621,983 bp, with a G+C content of 56.9%. This genomic analysis will be useful for understanding the metabolic activities of this asaccharolytic bacterium.

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Comparative Genomic Analysis Confirms Five Genetic Populations of the Select Agent, Rathayibacter toxicus

Microorganisms ◽

10.3390/microorganisms8030366 ◽

2020 ◽

Vol 8 (3) ◽

pp. 366

Author(s):

Jarred Yasuhara-Bell ◽

Mohammad Arif ◽

Grethel Y. Busot ◽

Rachel Mann ◽

Brendan Rodoni ◽

...

Keyword(s):

Genomic Analysis ◽

The United States ◽

Grass Species ◽

Comparative Genomic ◽

Underrepresented Populations ◽

System A ◽

Genome Wide ◽

The Family ◽

Study Support ◽

Genomic Regions

Rathayibacter toxicus is a Gram-positive, nematode-vectored bacterium that infects several grass species in the family Poaceae. Unique in its genus, R. toxicus has the smallest genome, possesses a complete CRISPR-Cas system, a vancomycin-resistance cassette, produces tunicamycin, a corynetoxin responsible for livestock deaths in Australia, and is designated a Select Agent in the United States. In-depth, genome-wide analyses performed in this study support the previously designated five genetic populations, with a core genome comprising approximately 80% of the genome for all populations. Results varied as a function of the type of analysis and when using different bioinformatics tools for the same analysis; e.g., some programs failed to identify specific genomic regions that were actually present. The software variance highlights the need to verify bioinformatics results by additional methods; e.g., PCR, mapping genes to genomes, use of multiple algorithms). These analyses suggest the following relationships among populations: RT-IV ↔ RT-I ↔ RT-II ↔ RT-III ↔ RT-V, with RT-IV and RT-V being the most unrelated. This is the most comprehensive analysis of R. toxicus that included populations RT-I and RT-V. Future studies require underrepresented populations and more recent isolates from varied hosts and geographic locations.

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Novel COL11A2 Pathogenic Variants in a Child with Autosomal Recessive Otospondylomegaepiphyseal Dysplasia: A Review of the Literature

Journal of Pediatric Genetics ◽

10.1055/s-0039-1698446 ◽

2019 ◽

Vol 09 (02) ◽

pp. 117-120

Author(s):

Pavalan Selvam ◽

Shekhar Singh ◽

Angita Jain ◽

Herjot Atwal ◽

Paldeep S. Atwal

Keyword(s):

Sequence Analysis ◽

Autosomal Recessive ◽

Autosomal Dominant ◽

Review Of The Literature ◽

Pathogenic Variants ◽

Phenotypic Spectrum ◽

Whole Exome ◽

The Family ◽

Type Xi Collagen ◽

Exome Sequence

AbstractOtospondylomegaepiphyseal dysplasia (OSMED) is an inherited autosomal dominant and recessive skeletal dysplasia caused by both heterozygous and homozygous pathogenic variants in COL11A2 encoding the α2(XI) collagen chains, a part of type XI collagen. Here, we describe a 2-year-old girl presenting from birth with a phenotype suggestive of OSMED. On whole exome sequence analysis of the family via commercially available methods, we detected two novel heterozygous pathogenic variants in the proband. In addition, we reviewed the phenotype of autosomal recessive OSMED cases with COL11A2 pathogenic variants reported to date and quantitatively highlighted the phenotypic spectrum.

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Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy

EP Europace ◽

10.1093/europace/euaa012 ◽

2020 ◽

Vol 22 (4) ◽

pp. 632-642 ◽

Cited By ~ 2

Author(s):

Gherardo Finocchiaro ◽

Harshil Dhutia ◽

Belinda Gray ◽

Bode Ensam ◽

Stathis Papatheodorou ◽

...

Keyword(s):

Ventricular Hypertrophy ◽

Clinical Phenotype ◽

Left Ventricular ◽

Disease Entity ◽

Long Qt ◽

Molecular Autopsy ◽

First Degree Relatives ◽

Pathogenic Variants ◽

The Family ◽

Qt Syndrome

Abstract Aims Idiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM. Methods and results Families of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff–Parkinson–White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family. Conclusion Idiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies.

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Characterization and genomic analysis of two Staphylococcus aureus bacteriophages isolated from poultry/livestock farms

Journal of General Virology ◽

10.1099/vir.0.053991-0 ◽

2013 ◽

Vol 94 (11) ◽

pp. 2569-2576 ◽

Cited By ~ 4

Author(s):

Hyunjin Yoon ◽

Jiae Yun ◽

Jeong-A Lim ◽

Eunjung Roh ◽

Kyu-Seok Jung ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Host Range ◽

Genomic Analysis ◽

Enzyme Treatment ◽

Comparative Genomic ◽

The Family ◽

Phage Dna ◽

Host Range Determination ◽

Range Determination ◽

Livestock Farms

Staphylococcus aureus is one of the most important pathogens, causing various diseases in humans and animals. As methicillin-resistant S. aureus (MRSA) has become increasingly prevalent, controlling this pathogen with standard antibiotic treatment has become challenging. Bacteriophages (phages) have attracted interest as alternative antibacterial agents to control MRSA. In this study, we isolated six S. aureus phages from soils of poultry/livestock farms. Based on the results of host range determination with 150 S. aureus strains and restriction enzyme treatment of phage DNA, two phages, designated SP5 and SP6, were selected for further characterization and genome sequencing. Both SP5 and SP6 were classified as members of the family Siphoviridae. The genome of SP5 comprises 43 305 bp and contains 63 ORFs, while the SP6 genome comprises 42 902 bp and contains 61 ORFs. Although they have different host spectra, the phage genomes exhibit high nucleotide similarity to each other. Adsorption assay results suggested that the host range determinants of the two phages are involved in both adsorption and infection. Comparative genomic analyses of the two phages provided evidence that the lysogenic/lytic control module and tail proteins may be important for host specificity.

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