Coexistence of a Homozygous Chromosome 4q35.2 Deletion and Hidden IQSEC2 Pathogenic Variant in a Child with Intellectual Disability.

Terminal deletions in the long arm of chromosome 4 are an uncommon event, with a worldwide incidence of approximately 0.001%. The majority of these deletions occur de novo. Terminal deletion cases are usually accompanied by clinical findings that include facial and cardiac anomalies, as well as intellectual disability. In this study, we describe the case of a 2-year-old girl, the fourth child born to consanguineous parents. While her karyotype was normal, a homozygous deletion was identified in the chromosome 4q35.2 region by subtelomeric FISH. A heterozygous deletion of the chromosome 4q35.2 region was observed in both parents. According to the literature, this is the first report of a case that has inherited a homozygous deletion of chromosome 4qter from carrier parents. Subsequent array-CGH analyses were performed on both the case and her parents. Whole-exome sequencing was also carried out to determine potential variants. We detected a NM_001111125.3:c.2329G>T (p.Glu777Ter) nonsense variant of the IQSEC2 gene in the girl, a variant that is related to X-linked intellectual disability.

Heterozygote Hemoglobin G-Coushatta as the Cause of a Falsely Decreased Hemoglobin A1C in an Ion-exchange HPLC Method.

Glycated hemoglobin (HbA1c) is used for the assessment of glycemic control in patients with diabetes. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA1c measurement. Here, we report two cases of Hemoglobin G-Coushatta (HBB:c.68A>C) variant that interferes in the measurement of HbA1c by a cation-exchange HPLC (CE-HPLC) method. HbA1c was measured by a CE-HPLC method in a Tosoh HLC-723 G7 instrument. The HbA1c levels were 2.9% and 4%. These results alerted us to a possible presence of hemoglobinopathy. In the hemoglobin variant analysis, HbA2 levels were detected as 78.3% and 40.7% by HPLC using the short program for the Biorad Variant II. HbA1c levels were measured by an immunoturbidimetric assay in a Siemens Dimension instrument. HbA1c levels were reported as 5.5% and 5.3%. DNA mutation analysis was performed to detect the abnormal hemoglobin variant. Presence of Hemoglobin G-Coushatta variant was detected in the patients. The Hb G-Coushatta variants have an impact on the determination of glycated hemoglobin levels using CEHPLC resulting in a false low value. Therefore, it is necessary to use another measurement method.

The effect of rs9939609 FTO gene polymorphism on weight loss after laparoscopic sleeve gastrectomy.

PURPOSE: Remarkable differences in weight loss have been observed in obese patients undergoing laparoscopic sleeve gastrectomy (LSG). These high variations might be partly explained by genetic factors. The rs9939609 fat mass and obesity-associated gene (FTO) polymorphism has been implicated in the susceptibility of obesity. We aimed to explore the effects of the rs9939609 FTO gene polymorphism on weight loss among severely obese patients applying for LSG. MATERIALS AND METHODS: All individuals were analyzed for the FTO rs9939609 gene polymorphism. A total of 74 morbid obese patients (20 male, 54 female) were operated. Body weight and body mass index (BMI) were measured at before LSG and after surgery at the sixth month. RESULTS: Twenty-eight patients (37.8%) had genotype TT (wild-type allel), 36 patients (48.6%) had genotype TA, and 10 patients (13.5%) had genotype AA. In both wild-type group and mutant group, BMI and weight levels decreased at the sixth month after surgery. Percent of excess weight loss (EWL) at 6 months of follow-up was similar in both groups. There were no differences between the mutant and wild-type groups percent of EWL at the sixth month after applying LSG. CONCLUSION: Our data showed that the rs9939609 FTO gene polymorphism is not a useful genetic test prior to LSG to help clinicians predicting the weight loss for severely obese patients in short-term follow-up.

ß-Thalassemia gene mutations in Antalya, Turkey: results from a single centre study.

ß-Thalassemia (ß-thal) is a common autosomal recessive disorder resulting from over 300 different mutations of the ß-globin genes. Our aim was to create a mutation map of ß-thal in the province of Antalya, Turkey. In this study, mutation analysis of a total 146 of ß-thal patients followed at the Thalassemia Center of the Antalya Education and Research Hospital, Antalya, Turkey, were included. Direct DNA sequence analysis was performed for mutation scanning of the ß-globin gene. One hundred and forty-six patients with ß-thal including all types were analyzed, and 14 different ß-thal mutations were detected. The most frequently seen mutation was HBB: c.93 - 21G > A [IVS-I-110 (G > A)] (52.7%), followed by HBB: .c.92 + 6T > C [IVS-I-6 (T > C)] (14.4%), HBB: c.-80T > A [-30 (T > A)] (8.2%), HBB: c.315 + 1G > A [IVS-II-1 (G > A)] (8.2%), which made up 83.1% of the observed mutations. Our results indicate the importance of micromapping and epidemiology studies of thalassemia, which will assist in establishing the national prevention and control program in Turkey.

Prenatal diagnosis of mosaic ring 22 duplication/deletion with terminal 22q13 deletion due to abnormal first trimester screening and choroid plexus cyst detected on ultrasound.

We report a rare case of mosaic ring chromosome 22 duplication/deletion in a fetus for whom karyotype analysis was required because of an abnormal finding in the maternal serum screening test and a choroid plexus cyst detected on prenatal ultrasound. Additional prenatal study of the amniotic fluid by fluorescence in situ hybridization was performed and the terminal 22q13.3 deletion was detected on ring chromosome. The final karyotype was 45,XX,-22[3]/46,XX,r(22)(p11q13.2)[63]/46,XX,idicr(22)(p11q13.2;p11q13.2)[2]dn.ishder(22)(N25+, ARSA-, ter-). The pegnancy was terminated. Cytogenetic analysis of the intracardiac blood also revealed ring 22 mosaicism with only one metaphase spread with idicr(22) as the unstable isodicentric rings are subsequently lost from most cells. We discuss the prenatal diagnosis of this rare condition.

CTLA4 gene polymorphisms in children and adolescents with autoimmune thyroid diseases.

Two common forms of autoimmune thyroid diseases are Graves' disease and Hashimoto's thyroiditis. Cytotoxic T lymphocyte antigen 4 (CTLA4) encoded by the CTLA4 gene on chromosome 2q33 plays a role in susceptibility to Graves' disease and is probably important also for Hashimoto's thyroiditis as well as for the other endocrine autoimmune disorders. The CTLA4 locus is the only nonhuman leukocyte antigen locus that has been found in association with Graves' disease repeatedly. Particularly, association of three polymorphic markers of CTLA4 gene, namely, C(-318)T, A49G, and (AT)n dinucleotide repeat, with Graves' disease was demonstrated in most of the population-based investigations. On the other hand, there are few studies to reveal the association of these markers with Hashimoto's thyroiditis. A49G polymorphism was proposed to be associated with Hashimoto's thyroiditis, and C(-318)T was suggested to be not associated. The patient groups consisted of 88 patients (10 males and 78 females; mean age: 14.5 +/- 3.2 years [4.6-21.0 years]) with a previous diagnosis of Hashimoto's thyroiditis and 112 euthyroid volunteers (51 males and 61 females; mean age: 14.1 +/- 2.9 years [5.2-18 years]). The frequency of A/G (A49G) genotype was high and statistically significant in patients with Hashimoto's thyroiditis in comparison with the control group. Although the frequency of C/T [C(-318)T] genotype is not significantly high in children with Hashimoto's thyroiditis according to the control group, the risk of Hashimoto's thyroiditis in A/G genotype group was 4.66 times greater than the group with A/A genotype. In this study, we documented that the A49G polymorphism might increase the susceptibility for Hashimoto's thyroiditis.