Akademik Veri Yönetim Sistemi
ESID 1st PID Care in development School, Zagreb, Hırvatistan, 15 - 17 Ekim 2022, ss.1
CASE
REPORT:
A 29-year-old male patient was
referred to our hospital due to low serum Ig levels. He was the fourth sibling of a
non-consanguineous family. In his family, his mother and maternal grandmother had
speech and hearing impairment associated with recurrent infections. The
pedigree was shown in Figure1. The patient had osteomyelitis at the age
of 18 months. He suffered from recurrent
pneumonia, soft tissue infections since his infancy. He was mentally retarded.
The physical examination revealed the absence of tonsils. His head
circumference was 54 cm (97 % percentile). Laboratory examination; showed
severe panhypogammaglobulinemia and low B cell count. Antibody responses to
diphtheria and tetanus vaccines were absent (Table1). A compound
heterozygous missense mutation in IKZF1 gene c.500A>G/ p. His 167Arg was detected.…
DISCUSSION:
In a cohort including six
different families with a history of recurrent bacterial infections of the
respiratory system, panhypogammaglobulinemia and autoimmune manifestations, heterozygous IKZF1 mutations have been
identified as an autosomal dominant type of inheritance(2). The patients have had
defects in both innate and adaptive immune systems, in addition to progressive
loss of B cells and functional anomalies of neutrophils, eosinophils, and
myeloid dendritic cells, as well as T cells and monocytes. These mutations in
IKZF1 reduce the DNA binding of IKAROS to its target sequence and give rise to
an immunodeficiency syndrome primarily characterized by an antibody deficiency (2). Patients with IKZF-1 deficiency differ from
CVID patients with other mutations by very low B cell counts, the
presence of CD27+ memory B cells and plasma cells, and a family history
consistent with autosomal dominant inheritance.Our patient had
late-onset recurrent infections,
panhypogammaglobulinemia, and severe B cell deficiency. His family history suggested
autosomal dominant inheritance.
Ikaros family members also take place in central nervous system
development. They are expressed in some striatal neurons. Alsio et al
showed that Ikaros is manifested mainly in early cortical progenitor cells and
improves early-born neuronal development in the
cerebral cortex (3). The gene coding cereblon
(CRBN) which has an important role related to memory
and learning processes was identified in patients with mild autosomal
recessive intellectual disability (4,5). A study showed that CRBN binds to Ikaros by
the N-terminal region and functions as a transcriptional modulator of Ikaros in
the nucleus(5).
Our
patient had mental development delay since his
infancy and no history of central nervous system infection.
According to the EGY intelligence test result (IQ: 64), the patient was
accepted as mild intellectual disability (MID). He had also obsessive-compulsive
compulsions and prominent cognitive dysfunction. Recurrent
infections and mental retardation were also present in her mother and
grandmother. Although genetic
testing of the mother and the grandmother could not be done, it was thought
that they might have IKZ deficiency because of their intellectual limitations
and frequent infections.
Despite the fact that the effect of the IKZF1 gene on brain development and cognitive functions on a cellular basis has been emphasized in the literature, no comment has been made on the mental status of patients with Ikaros defects. With this article, we wanted to draw attention to the impact of IKZF1 deficiency not only on immunodeficiency but also cognitive functions.