Immune Deficiency in Jacobsen Syndrome: Molecular and Phenotypic Characterization
Por:
Rodriguez-Lopez, Raquel, Gimeno-Ferrer, Fatima, Montesinos, Elena, Ferrer-Bolufer, Irene, Guzman Lujan, Carola, Albuquerque, David, Monzo Cataluna, Carolina, Ballesteros, Virginia, Perez-Gramunt, Monserrat Aleu
Publicada:
1 ago 2021
Resumen:
Jacobsen syndrome or JBS (OMIM #147791) is a contiguous gene syndrome
caused by a deletion affecting the terminal q region of chromosome 11.
The phenotype of patients with JBS is a specific syndromic phenotype
predominately associated with hematological alterations. Complete and
partial JBS are differentiated depending on which functional and causal
genes are haploinsufficient in the patient. We describe the case of a
6-year-old Bulgarian boy in which it was possible to identify all of the
major signs and symptoms listed by the Online Mendelian Inheritance in
Man (OMIM) catalog using the Human Phenotype Ontology (HPO). Extensive
blood and marrow tests revealed the existence of thrombocytopenia and
leucopenia, specifically due to low levels of T and B cells and low
levels of IgM. Genetic analysis using whole-genome single nucleotide
polymorphisms (SNPs)/copy number variations (CNVs) microarray
hybridization confirmed that the patient had the deletion
arr[hg19]11q24.3q25(128,137,532-134,938,470)x1 in heterozygosis. This
alteration was considered causal of partial JBS because the essential
BSX and NRGN genes were not included, though 30 of the 96 HPO
identifiers associated with this OMIM were identified in the patient.
The deletion of the FLI-1, ETS1, JAM3 and THYN1 genes was considered to
be directly associated with the immunodeficiency exhibited by the
patient. Although immunodeficiency is widely accepted as a major sign of
JBS, only constipation, bone marrow hypocellularity and recurrent
respiratory infections have been included in the HPO as terms used to
refer to the immunological defects in JBS. Exhaustive functional
analysis and individual monitoring are required and should be mandatory
for these patients.
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