Title:Novel DNMT3B Mutation in a Patient with Immunodeficiency, Centromeric
Instability, and Facial Anomalies (ICF) Syndrome and a Bronchopulmonary
Collateral Artery
Volume: 23
Issue: 3
Author(s): Arya Aminorroaya, Elham Rayzan, Sepideh Shahkarami, Simin Seyedpour, Samaneh Zoghi, Zahra Aryan, Ido Somekh, Meino Rohlfs, Christoph Klein, Hossein Esmaeilzadeh*Nima Rezaei*
Affiliation:
- Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Allergy and Clinical Immunology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
- Research Center
for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
Keywords:
Immunodeficiency syndrome, variable, DNA methyltransferase 3B, primary immunodeficiency diseases, heart defects, congenital, collateral artery, bronchopulmonary collateral artery.
Abstract:
Background: Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome
is a rare autosomal recessive disorder. ICF1 is caused by bi-allelic mutations in the gene encoding
deoxyribonucleic acid methyltransferase-3B (DNMT3B). Herein, we report a novel homozygous
DNMT3B mutation in a patient with ICF1.
Case Presentation: An eight-month-old Iranian Caucasian infant of consanguineous 1st-degree cousins
presented to our clinic for evaluation of neutropenia. Physical examination was unremarkable
except for low-set ears and a systolic cardiac murmur. He had a history of recurrent respiratory infections
and oral thrush. Moreover, a collateral artery between the bronchial and pulmonary arteries
was observed on the angiogram, mimicking a patent ductus arteriosus on the echocardiogram. Growth
percentiles were normal; however, he had a neurodevelopmental delay. Family history was significant
for a sibling who deceased at nine months of age after recurrent respiratory infections. Laboratory
evaluation revealed a normal white blood cell count with neutropenia and normal bone marrow
studies. He had hypogammaglobinemia with normal flow cytometric studies and was treated with
prophylactic trimethoprim-sulfamethoxazole and itraconazole. After that, he was re-admitted three
times due to recurrent episodes of pneumonia and an episode of pseudomonas aeruginosa meningitis.
Currently, he is five years old and doing well on monthly intravenous immunoglobulin. Due to recurrent
infections, hypogammaglobulinemia, and neutropenia, as well as a family history of consanguinity
and a sibling who deceased during infancy, a primary immune deficiency was suspected.
Genetic studies utilizing whole-exome sequencing demonstrated a homozygous missense mutation
in DNMT3B (LRG_56t1:c.2008C>T; p.Arg670Trp) in the patient studied. The mutation has not been
previously reported.
Conclusion: We describe a novel homozygous DNMT3B mutation in an Iranian boy with ICF1. It is
associated with recurrent infections, hypogammaglobinemia, neutropenia, mild facial anomalies, and
a bronchopulmonary collateral artery.
