Molecular characterization of an intronic RNASEH2B variant in a patient with Aicardi-Goutières syndrome.

Aicardi-Goutières syndrome (AGS) is a progressive multisystem disorder including encephalopathy with significant impacts on intellectual and physical abilities. An early diagnosis is becoming ever more crucial, as targeted therapies are emerging. A deep understanding of the molecular heterogeneity of AGS can help guide the early diagnosis and clinical management of patients, and inform recurrence risks.

Systemic Presentation of Somatic TET2 Mutated B-Cell Lymphoma in a Child With Kabuki Syndrome and a Germline KMT2D Variant.

Objectives: Kabuki syndrome (KS) is a rare congenital malformation syndrome associated with germline KMT2D mutations. Recurrent somatic mutations in KMT2D have frequently been observed in B-cell lymphoma, but limited studies are available that evaluate the genetic landscape of B-cell lymphomas in the setting of KS.

Methods: We describe a unique case of B-cell lymphoma that illustrates histologic features of pediatric-type follicular lymphoma (FL) in a young patient with KS and autoimmune disease who showed a systemic presentation of widespread lymphadenopathy and clonal lymphocytosis.

Comparing the attitudes of physicians and non-physicians toward communicating a patient's BRCA1 mutation to a first-degree relative against a patient's wishes.

Although genetic testing can be vastly informative, it creates a dilemma if a patient does not want to disclose an abnormal genetic test to at-risk relatives. A sample of 200 participants from Nevada (100 physicians, 100 non-physicians) completed an 11-item questionnaire asking demographic information, familiarity with genetics and genetic testing, and opinions about a physician's role in a hypothetical case in which a patient does not wish to communicate her BRCA1 mutation to her sister. Although most respondents did not think the physician should notify the sister against the patient's wishes, more non-physicians (40%) than physicians (23%) contended that the physician should do so (p = 0.

Placental proteins with predicted roles in fetal development decrease in premature infants.

Background: Emerging evidence from animal experiments indicate that factors secreted by the placenta are critical for normal fetal organ development. Our objective was to characterize the umbilical vein and artery proteome in preterm infants and identify proteins that decrease in the neonatal circulation following delivery.

Methods: Cord blood at delivery and neonatal blood at 48-72 h of life was collected in 25 preterm infants.

When Childhood Cancer Becomes a Family Affair, It Really Hits Home.

In this article, a father and son describe the experience of childhood leukemia treatment and its aftermath with the unique perspective of a parent who is also a pediatric oncologist. An illness that began with an apparently favorable prognosis was transformed by an early relapse, followed by unexpected complications and difficult treatment decisions. Despite unfavorable statistics, the son is a long-term survivor with an overall excellent quality of life, despite several late events and effects.

Mantle Cell Lymphoma Presenting as a Subcutaneous Mass of the Right Leg.

Mantle cell lymphoma (MCL) is a relatively rare B-cell non-Hodgkin lymphoma, typically presenting with extensive lymphadenopathy, bone marrow involvement, and splenomegaly. Extranodal sites can also be involved. We discuss a 73-year-old man whose MCL presented with a 6-month history of a subdermal mass of the right upper thigh and no systemic symptoms.

Multifocal Stroke Complicating Anti-NMDA Receptor Encephalitis.

Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) is an autoimmune form of encephalitis, first described in 2005 and now recognized as among the more common causes of encephalitis. While NMDARE can result in permanent neurologic deficits or even mortality, the prognosis in children is generally more favorable; 75-85% of children and teenagers achieve a full or substantial recovery. We describe here a preadolescent female, whose course of NMDARE was complicated by a unilateral stroke, resulting in permanent deficits.

Further Characterization of Hb Bronovo [α103(G10)His→Leu; : c.311A>T] and First Report of the Homozygous State.

Hb Bronovo [α103(G10)His→Leu, : c.311A>T] is an α-globin variant that interferes with and decreases binding efficiency to α hemoglobin (Hb) stabilizing protein (AHSP), a chaperone molecule. The histidine residue at position 103 is integral to the AHSP hydrogen bond formation where disruption results in an increased quantity of cytotoxic free α-globin chains, thereby creating a similar pathophysiology as β-thalassemia (β-thal).

Acute associations between PM and ozone concentrations and asthma exacerbations among patients with and without allergic comorbidities.

Acute effects of outdoor air pollution on asthma exacerbations may vary by asthma phenotype (allergic vs nonallergic). Associations of ambient PM and ozone concentrations with acute asthma visits (office, urgent, emergency, and hospitalization) were investigated using electronic medical records. International Classification of Disease codes were used to identify asthmatics, and classify them based on the presence or absence of an allergic comorbidity in their medical records.

Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors.

Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra-abdominally, and are defined by EWSR1-WT1 gene fusion. Intracranial DSRCTs are exceptionally rare with only seven previously reported fusion-positive cases. Herein, we evaluate the clinical, morphologic, immunohistochemical and molecular features of five additional examples.

A novel p.Gly187Arg TP53 variant appears to result in Li-Fraumeni syndrome.

Li-Fraumeni syndrome is an autosomal dominant cancer syndrome characterized by pathogenic variants in the TP53 gene on chromosome 17. The most common cancers in Li-Fraumeni kindreds include sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma. We report a 9-month-old male who was diagnosed with an adrenocortical tumor and later found to harbor a novel TP53 c.

Agalsidase alfa in pediatric patients with Fabry disease: a 6.5-year open-label follow-up study.

Background: Signs and symptoms of the X-linked disorder, Fabry disease (FD), can occur early during childhood with heterogeneous clinical manifestations including potential cardiac and renal dysfunction. Several studies support the efficacy of the enzyme replacement therapy (ERT) agalsidase alfa, in adults with FD, though published data on the long-term safety and efficacy of agalsidase alfa in children are limited. As early treatment with ERT has the potential to reduce complications arising from disease progression, children in particular could benefit.