Structural variation and missense mutation in SBDS associated with Shwachman-Diamond syndrome.

BACKGROUND: Shwachman-Diamond syndrome (SDS) is an autosomal recessive ribosomopathy caused mainly by compound heterozygous mutations in SBDS. Structural variation (SV) involving the SBDS locus has been rarely reported in association with the disease. We aimed to determine whether an SV contributed to the pathogenesis of a case lacking biallelic SBDS point mutations. CASE PRESENTATION: Whole exome sequencing was performed in a patient with SDS lacking biallelic SBDS point mutations. Array comparative genomic hybridization and Southern blotting were used to seek SVs across the SBDS locus. Locus-specific polymerase chain reaction (PCR) encompassing flanking intronic sequence was also performed to investigate mutation within the locus. RNA expression and Western blotting were performed to analyze allele and protein expression. We found the child harbored a single missense mutation in SBDS (c.98A > C; p.K33T), inherited from the mother, and an SV in the SBDS locus, inherited from the father. The missense allele and SV segregated in accordance with Mendelian expectations for autosomal recessive SDS. Complementary DNA and western blotting analysis and locus specific PCR support the contention that the SV perturbed SBDS protein expression in the father and child. CONCLUSION: Our findings implicate genomic rearrangements in the pathogenesis of some cases of SDS and support patients lacking biallelic SBDS point mutations be tested for SV within the SBDS locus.

Marrow: red, yellow and bad.

Bone marrow is one of the largest and most dynamic tissues in the body, and it is well-depicted on conventional MRI sequences. However, often only perfunctory attention is paid to the bone marrow on musculoskeletal imaging studies, raising the risk of delayed or missed diagnoses. To guide appropriate recognition of normal variants and pathological processes involving the marrow compartment, this article describes and depicts the physiological spatiotemporal pattern of conversion of hematopoietic red marrow to fatty yellow marrow during childhood and adolescence, and the characteristic imaging findings of disorders involving marrow hyperplasia/reconversion, marrow infiltration/deposition and marrow depletion/failure.

Improvement in Pulmonary Function Following Discontinuation of Vaping or E-Cigarette Use in Adolescents with EVALI.

Introduction: In 2019, an alarming number of cases coined as e-cigarette, or vaping, product use-associated lung injury (EVALI) were described in adolescents ranging from mild respiratory distress to fulminant respiratory failure. Limited data have been published on outcomes at short-term follow-up. We aimed to describe pulmonary manifestations, function, and radiologic findings after corticosteroid therapy in a cohort of adolescent patients. Methods: A retrospective chart analysis of all patients presenting to our institution between July 2019 and December 2019 with EVALI was conducted. Patients who had pulmonary follow-up were included. Spirometry was performed before discharge from the hospital and during outpatient follow-up. A paired t-test was used to compare serial spirometry data between visits. Results: Eight patients (6 males) were included. Two patients required intubation with mechanical ventilation, 2 required bilevel positive airway pressure, and 3 required oxygen supplementation. All patients received glucocorticoids (3 receiving pulse dosing). Initial spirometry revealed decreased forced expiratory volume in one second and forced vital capacity with clinically and statistically significant improvement at follow-up (mean follow-up was 46.5 days). Radiographic manifestations also improved after vaping was discontinued. Conclusion: In our cohort of patients with EVALI, at short-term follow-up, all normalized their spirometry parameters and showed clinical resolution of symptoms.

Cellular mesoblastic nephroma (infantile renal fibrosarcoma): institutional review of the clinical, diagnostic imaging, and pathologic features of a distinctive neoplasm of infancy.

BACKGROUND: Cellular mesoblastic nephroma has been associated with a more aggressive course than classic mesoblastic nephroma, including local recurrences and metastases. OBJECTIVE: To define the clinicopathologic and imaging features distinguishing cellular from classic mesoblastic nephroma. MATERIALS AND METHODS: Retrospective review of clinical charts and imaging studies of ten children with mesoblastic nephroma from 1996 to 2007 at a large children's hospital. RESULTS: In six children the mesoblastic nephroma was pure cellular, in two mixed, and in two classic. The mean ages at diagnosis were 107 days for those with the cellular form, and 32 days for those with the classic form. Hypoechoic or low-attenuation regions representing necrosis or hemorrhage were found in all children with the cellular form and in none of those with the classic form. Hypertension was present in 70% and hypercalcemia in 20% of the children and resolved following nephrectomy. Two cellular tumors encased major abdominal vessels. Local recurrence and metastases occurred within 6 months of tumor resection in two children with the cellular form. Intraspinal extension and intratumoral pseudoaneurysm were seen in one child with the cellular form. The cellular tumors shared histopathologic features with infantile fibrosarcoma (IFS), and RT-PCR testing in two children with the cellular form revealed the t(12;15) ETV6-NTRK3 gene fusion common to IFS. CONCLUSION: Distinct from the classic form, cellular mesoblastic nephroma is more heterogeneous in appearance on imaging, tends to be larger and present later in infancy, and can exhibit aggressive behavior including vascular encasement and metastasis. Intraspinal extension and intratumoral pseudoaneurysm are previously unreported findings encountered in our cellular mesoblastic nephroma series. The shared histopathology and translocation gene fusion support the concept of cellular mesoblastic nephroma as the renal form of IFS.