Extended List of Warning Signs in Qualification to Diagnosis and Treatment of Inborn Errors of Immunity in Children and Young Adults

Dąbrowska, Anna; Grześk, Elżbieta; Urbańczyk, Anna; Mazalon, Marta; Grześk, Grzegorz; Styczyński, Jan; Kołtan, Sylwia

doi:10.3390/jcm12103401

Cited by 5 publications

(1 citation statement)

References 42 publications

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“…Patient 4 had ≥2 bouts of pneumonia in one year. Skin abnormalities including eczema, skin rashes, and keratosis were found in patients 2 and 5, and they are increasingly being recognized as warning signs in patients with primary immunodeficiency [30,31]. Allergic manifestations in patients with primary immunodeficiency include food allergies and asthma, which were both found in patient 5 [32].…”

Section: Craniofacial Abnormalities Microcephalymentioning

confidence: 99%

Novel Genetic and Phenotypic Expansion in Ameliorated PUF60-Related Disorders

Baum,

Huang,

Vincent-Delorme

et al. 2024

IJMS

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Heterozygous variants in the Poly(U) Binding Splicing Factor 60kDa gene (PUF60) have been associated with Verheij syndrome, which has the key features of coloboma, short stature, skeletal abnormalities, developmental delay, palatal abnormalities, and congenital heart and kidney defects. Here, we report five novel patients from unrelated families with PUF60-related disorders exhibiting novel genetic and clinical findings with three truncating variants, one splice-site variant with likely reduced protein expression, and one missense variant. Protein modeling of the patient’s missense variant in the PUF60 AlphaFold structure revealed a loss of polar bonds to the surrounding residues. Neurodevelopmental disorders were present in all patients, with variability in speech, motor, cognitive, social-emotional and behavioral features. Novel phenotypic expansions included movement disorders as well as immunological findings with recurrent respiratory, urinary and ear infections, atopic diseases, and skin abnormalities. We discuss the role of PUF60 in immunity with and without infection based on recent organismic and cellular studies. As our five patients showed less-severe phenotypes than classical Verheij syndrome, particularly with the absence of key features such as coloboma or palatal abnormalities, we propose a reclassification as PUF60-related neurodevelopmental disorders with multi-system involvement. These findings will aid in the genetic counseling of patients and families.

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Section: Craniofacial Abnormalities Microcephalymentioning

confidence: 99%

Novel Genetic and Phenotypic Expansion in Ameliorated PUF60-Related Disorders

Baum,

Huang,

Vincent-Delorme

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity

Segura-Tudela,

López-Nevado,

Nieto-López

et al. 2024

J Clin Immunol

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Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect.

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