Tuba Turul Ozgur

Additional Diverse Findings Expand the Clinical Presentation of DOCK8 Deficiency

We describe seven Turkish children with DOCK8 deficiency who have not been previously reported. Three patients presented with typical features of recurrent or severe cutaneous viral infections, atopic dermatitis, and recurrent respiratory or gastrointestinal tract infections. However, four patients presented with other features. Patient 1–1 featured sclerosing cholangitis and colitis; patient 2–1, granulomatous soft tissue lesion and central nervous system involvement, with primary central nervous system lymphoma found on follow-up; patient 3–1, a fatal metastatic leiomyosarcoma; and patient 4–2 showed no other symptoms initially besides atopic dermatitis. Similar to other previously reported Turkish patients, but in contrast to patients of non-Turkish ethnicity, the patients’ lymphopenia was primarily restricted to CD4+ T cells. Patients had homozygous mutations in DOCK8 that altered splicing, introduced premature terminations, destabilized protein, or involved large deletions within the gene. Genotyping of remaining family members showed that DOCK8 deficiency is a fully penetrant, autosomal recessive disease. In our patients, bone marrow transplantation resulted in rapid improvement followed by disappearance of viral skin lesions, including lesions resembling epidermodysplasia verruciformis, atopic dermatitis, and recurrent infections. Particularly for patients who feature unusual clinical manifestations, immunological testing, in conjunction with genetic testing, can prove invaluable in diagnosing DOCK8 deficiency and providing potentially curative treatment.

Six different CYBA mutations including three novel mutations in ten families from Turkey, resulting in autosomal recessive chronic granulomatous disease

Backgroundu2002 One of the rarest forms of autosomal recessive chronic granulomatous disease (AR‐CGD) is attributable to mutations in the CYBA gene, which encodes the alpha polypeptide of cytochrome b558, (also known as p22‐phox), a key transmembrane protein in the phagocyte NADPH oxidase system. This gene is localized on chromosome 16q24, encompasses 8·5u2003kb and contains six exons.

Hematopoietic stem cell transplantation in a CD3γ-deficient infant with inflammatory bowel disease

Abstract:u2002 Partial or total CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain are among the autosomally inherited SCID presenting with T−B+NK+ phenotype with lymphopenia. The clinical findings are generally severe in all except for CD3 gamma deficiency. Here we present a 10‐month‐old CD3 gamma deficient boy with IBD. The patient had suffered from intractable diarrhea, recurrent pulmonary infections and oral moniliasis since two months of age. Following the first allogeneic HSCT from his HLA‐identical (6/6) sister after a reduced intensity regimen, a second transplantation was performed five months later. On day +19 after second transplantation, the CD3 TCR alfa/beta chain expression increased to 66% with development of full donor chimerism (98.6%). A significant improvement in diarrhea, perianal lesions, and rectal fistula was observed suggesting an improvement in inflammatory bowel disease. The patient died at home on day +50 with a sudden respiratory failure secondary to an undetermined infection. The case was interesting being the first reported case with SCID and inflammatory bowel disease who responded very well to HSCT by full recovery of intractable diarrhea, failure to thrive, laboratory findings, and improvement of fistula formation.

Two SCID cases with Cernunnos-XLF deficiency successfully treated by hematopoietic stem cell transplantation

Çağdaş D, Özgür TT, Asal GT, Revy P, De Villartay J‐P, van der Burg M, Sanal Ö, Tezcan İ. Two SCID cases with Cernunnos‐XLF deficiency successfully treated by hematopoietic stem cell transplantation.

Griscelli syndrome types 1 and 3: analysis of four new cases and long-term evaluation of previously diagnosed patients

Griscelli syndrome (GS) is a rare autosomal recessive disorder characterized by partial albinism. Three different types are caused by defects in three different genes. Patients with GS type 1 have primary central nervous system dysfunction, type 2 patients commonly develop hemophagocytic lymphohistiocytosis, and type 3 patients have only partial albinism. While hematopoietic stem cell transplantation is life saving in type 2, no specific therapy is required for types 1 and 3. Patients with GS types 1 and 3 are very rare. To date, only 2 patients with type 3 and about 20 GS type 1 patients, including the patients described as Elejalde syndrome, have been reported. The neurological deficits in Elejalde syndrome were reported as severe neurodevelopmental delay, seizures, hypotonia, and ophthalmological problems including nystagmus, diplopia, and retinal problems. However, none of these patients’ clinical progresses were reported. We described here our two new type 1 and two type 3 patients along with the progresses of our previously diagnosed patients with GS types 1 and 3. Our previous patient with GS type I is alive at age 21 without any other problems except severe mental and motor retardation, patients with type 3 are healthy at ages 21 and 24xa0years having only pigmentary dilution; silvery gray hair, eye brows, and eyelashes. Since prognosis, treatment options, and genetic counseling markedly differ among different types, molecular characterization has utmost importance in GS.

Four different NCF2 mutations in six families from Turkey and an overview of NCF2 gene mutations

Backgroundu2002 One of the rarest forms of autosomal recessive chronic granulomatous disease (AR‐CGD) is attributable to mutations in the NCF2 gene, which encodes the polypeptide p67phox, a key cytoplasmic protein in the phagocyte NADPH oxidase system. NCF2 is localized on chromosome 1q25, encompasses 40u2003kb and contains 16 exons.

Atypical combined immunodeficiency due to Artemis defect: A case presenting as hyperimmunoglobulin M syndrome and with LGLL

SCID can be caused by various genetic mutations leading to distinctive phenotypes according to the presence of T, B and NK cells. Artemis is a gene encoded on chromosome 10p. The deficiency of this molecule causes an inability to repair DNA double strand breaks and is one of the causes of radiosensitive T-B-NK+ SCID. The syndrome usually presents with opportunistic infections in the first years of life that leads to death if not treated with stem cell transplantation. The spectrum of the disease can be wide because of the heterogeneity of the mutations. Herein we present an atypical SCID (CID) patient with Artemis defect mimicking hyper IgM syndrome. Our patient had high serum IgM with low IgG and IgA levels, lymphocytosis and recurrent infections, intractable diarrhea, growth retardation, systemic CMV infection and sclerosing cholangitis. He also developed large granular lymphocytic leukemia and survived until the age of 6.5 years.

A novel mutation in TAP1 gene leading to MHC class I deficiency: Report of two cases and review of the literature

Major histocompatibility complex (MHC) class I deficiency syndrome is a rare primary immunodeficiency caused by mutations in the peptide transporter complex associated with antigen presentation (TAP) gene which plays a crucial role in intracellular peptide antigen presentation. A few cases have been reported to date. Recurrent sinopulmonary infections and skin ulcers are the main characteristics of the syndrome. Here we report two siblings diagnosed with TAP1 deficiency syndrome associated only with recurrent sinopulmonary infections with the description of a novel mutation leading to a premature stop codon in TAP1 gene and review of the relevant literature. Both of the siblings had recurrent sinopulmonary infections since childhood, responded to antibiotherapy well, neither of them had hospitalization history because of infections. One had chronic hepatitis B infection which may possibly be related to TAP1 gene defect.

Progressive neurodegenerative syndrome in a patient with X-linked agammaglobulinemia receiving intravenous immunoglobulin therapy.

A progressive encephalopathy of unknown etiology has been described in patients with primary immunodeficiency disorders. In this report, we characterize the clinical features of this progressive neurodegenerative dementing disorder in a young man with Bruton agammaglobulinemia, through neuropsychological tests and a video sequence. The clinical course of the encephalopathy seems rather uniform: Cognition, especially frontal lobe function, is affected in the early stages, and some patients develop movement disorders. The syndrome causes severe cognitive and physical disability, and can eventually be fatal. The autoimmunity results from dysregulated immune responses, but the underlying mechanism has not yet been fully explained.

Clinical and genetic features of the patients with X-Linked agammaglobulinemia from Turkey: Single-centre experience

X‐linked agammaglobulinemia is a primary immunodeficiency disorder resulting from BTK gene mutations. There are many studies in the literature suggesting contradictory ideas about phenotype‐genotype correlation. The aim of this study was to identify the mutations and clinical findings of patients with XLA in Turkey, to determine long‐term complications related to the disease and to analyse the phenotype‐genotype correlation. Thirty‐two patients with XLA diagnosed between 1985 and 2016 in Pediatric Immunology Department of Hacettepe University Ihsan Dogramaci Childrens Hospital were investigated. A clinical survey including clinical features of the patients was completed, and thirty‐two patients from 26 different families were included in the study. Getting early diagnosis and regular assessment with imaging techniques seem to be the most important issues for improving the health status of the patients with XLA. Early molecular analysis gives chance for definitive diagnosis and genetic counselling, but not for predicting the clinical severity and prognosis.