Derivative chromosome 1 and GLUT1 deficiency syndrome in a sibling pair

<p>Abstract</p> <p>Background</p> <p>Genomic imbalances constitute a major cause of congenital and developmental abnormalities. GLUT1 deficiency syndrome is caused by various de novo mutations in the facilitated human glucose transporter 1 gene (1p34.2) and patients with this syndrome have been diagnosed with hypoglycorrhachia, mental and developmental delay, microcephaly and seizures. Furthermore, 1q terminal deletions have been submitted in the recent reports and the absence of corpus callosum has been related to the deletion between <it>C1orf100 </it>and <it>C1orf121 </it>in 1q44.</p> <p>Results</p> <p>This study reports on a sibling pair with developmental delay, mental retardation, microcephaly, hypotonia, epilepsy, facial dysmorphism, ataxia and impaired speech. Chromosome analysis revealed a derivative chromosome 1 in both patients. FISH and MCB analysis showed two interstitial deletions at 1p34.2 and 1q44. SNP array and array-CGH analysis also determined the sizes of deletions detailed. The deleted region on 1p34.2 encompasses 33 genes, among which is <it>GLUT1 </it>gene (<it>SLC2A1</it>). However, the deleted region on 1q44 includes 59 genes and distal-proximal breakpoints were located in the ZNF672 gene and SMYD3 gene, respectively.</p> <p>Conclusion</p> <p>Haploinsufficiency of <it>GLUT1 </it>leads to GLUT1 deficiency syndrome, consistent with the phenotype in patients of this study. Conversely, in the deleted region on 1q44, none of the genes are related to findings in these patients. Additionally, the results confirm previous reports on that corpus callosal development may depend on the critical gene(s) lying in 1q44 proximal to the <it>SMYD3 </it>gene.</p

A pilot study for genome wide association study (GWAS) in patients with juvenile idiopathic arthritis (JIA) and their parents

PubMe

Interaction between dietary fat intake and metabolic genetic risk score on 25-hydroxyvitamin D concentrations in a Turkish adult population

Previous studies have pointed out a link between vitamin D status and metabolic traits, however, consistent evidence has not been provided yet. This cross-sectional study has used a nutrigenetic approach to investigate the interaction between metabolic-genetic risk score (GRS) and dietary intake on serum 25-hydroxyvitamin D [25(OH)D] concentrations in 396 unrelated Turkish adults, aged 24–50 years. Serum 25(OH)D concentration was significantly lower in those with a metabolic-GRS ≥ 1 risk allele than those with a metabolic-GRS < 1 risk allele (p = 0.020). A significant interaction between metabolic-GRS and dietary fat intake (energy%) on serum 25(OH)D levels was identified (Pinteraction = 0.040). Participants carrying a metabolic-GRS ≥ 1 risk allele and consuming a high fat diet (≥38% of energy = 122.3 ± 52.51 g/day) had significantly lower serum 25(OH)D concentration (p = 0.006) in comparison to those consuming a low-fat diet (<38% of energy = 82.5 ± 37.36 g/d). In conclusion, our study suggests a novel interaction between metabolic-GRS and dietary fat intake on serum 25(OH)D level, which emphasises that following the current dietary fat intake recommendation (<35% total fat) could be important in reducing the prevalence of vitamin D deficiency in this Turkish population. Nevertheless, further larger studies are needed to verify this interaction, before implementing personalized dietary recommendations for the maintenance of optimal vitamin D status

Interaction between Dietary Fat Intake and Metabolic Genetic Risk Score on 25-Hydroxyvitamin D Concentrations in a Turkish Adult Population

From MDPI via Jisc Publications RouterHistory: accepted 2022-01-14, pub-electronic 2022-01-17Publication status: PublishedFunder: Scientific and Technological Research Council of Turkey; Grant(s): 216S272Previous studies have pointed out a link between vitamin D status and metabolic traits, however, consistent evidence has not been provided yet. This cross-sectional study has used a nutrigenetic approach to investigate the interaction between metabolic-genetic risk score (GRS) and dietary intake on serum 25-hydroxyvitamin D [25(OH)D] concentrations in 396 unrelated Turkish adults, aged 24−50 years. Serum 25(OH)D concentration was significantly lower in those with a metabolic-GRS ≥ 1 risk allele than those with a metabolic-GRS 1 risk allele (p = 0.020). A significant interaction between metabolic-GRS and dietary fat intake (energy%) on serum 25(OH)D levels was identified (Pinteraction = 0.040). Participants carrying a metabolic-GRS ≥ 1 risk allele and consuming a high fat diet (≥38% of energy = 122.3 ± 52.51 g/day) had significantly lower serum 25(OH)D concentration (p = 0.006) in comparison to those consuming a low-fat diet (38% of energy = 82.5 ± 37.36 g/d). In conclusion, our study suggests a novel interaction between metabolic-GRS and dietary fat intake on serum 25(OH)D level, which emphasises that following the current dietary fat intake recommendation (35% total fat) could be important in reducing the prevalence of vitamin D deficiency in this Turkish population. Nevertheless, further larger studies are needed to verify this interaction, before implementing personalized dietary recommendations for the maintenance of optimal vitamin D status

FTO gene-lifestyle interactions on serum adiponectin concentrations and central obesity in a Turkish population

The aim of the study was to investigate whether lifestyle factors modify the association fat mass and obesity-associated (FTO) gene single nucleotide polymorphisms (SNPs) and obesity in a Turkish population. The study included 400 unrelated individuals, aged 24-50 years recruited in a hospital setting. Dietary intake and physical activity were assessed using 24-hour dietary recall and self-report questionnaire, respectively. A genetic risk score (GRS) was developed using FTO SNPs, rs9939609 and rs10163409. Body mass index and fat mass index were significantly associated with FTO SNP rs9939609 (P=0.001 and P=0.002, respectively) and GRS (P=0.002 and P=0.003, respectively). The interactions between SNP rs9939609 and physical activity on adiponectin concentrations, and SNP rs10163409 and dietary protein intake on increased waist circumference were statistically significant (Pinteraction=0.027 and Pinteraction=0.044, respectively). This study demonstrated that the association between FTO SNPs and central obesity might be modified by lifestyle factors in this Turkish population

Evaluation Of Pregnancies In 25 Families With Balanced/Unbalanced Chromosomal Translocations

The researchers evaluated pregnancies in families with balanced/unbalanced translocations. This clinical cohort consisted of 25 pregnancies with balanced/unbalanced chromosomal translocations in family member(s) (maternal, paternal, fetal, abortion material, and/or previous fetus(es)) who underwent prenatal diagnosis. Translocations were observed in 18 cases (14 balanced and 4 unbalanced translocations). The researchers found 2 and 12 cases among the chromosomal translocations were paternal and maternal in origin, respectively. The researchers demonstrated that parent karyotypes were normal in 4 cases, while only maternal karyotypes were normal in 3 cases with unknown paternal karyotypes. Five of the prenatally diagnosed chromosomal abnormalities were Robertsonian and 13 were reciprocal translocations, Among the Robertsonian translocations, 2 were unbalanced. Early fetal loss or recurrent miscarriages were observed in previous history of 10(40%) and 6(24%) respectively. Prenatal diagnosis is critical in pregnancies with balanced/unbalanced chromosomal translocations in a member(s) of the family or those with poor gestational histories.Wo

Cyp1A1 Gene Polymorphism And Polycystic Ovary Syndrome

The aim of this study was to assess the rates of variant alleles of cytochrome P4501A1 (CYP1A1) in patients with polycystic ovary syndrome (PCOS). It was designed as a case-control study in Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology and Genetics. Forty-eight patients with PCOS served as the study group. Ninety-six regularly cycling women with no clinical and biochemical evidence of hyperandrogenism and polycystic ovary appearance served as the controls. The CYP1A1 variant alleles of all patients were determined via polymerase chain reaction. The rate of the CYP1A1 isoleucine (Ile)/valine (Val) allele was significantly higher in patients with PCOS than in the controls (OR: 7.8, 95% CI: 3.45-17.52, P < 0.001). However, there was no statistically significant difference in the distribution of Val/Val genotype (OR: 4.0, 95% CI: , 0.60-26.73). The rate of any Val genotype (Ile/Val or Val/Val) was significantly higher in patients with PCOS compared with the control group (OR: 7.4, 95% CI: 3.33-16.46, P < 0.001). In conclusion, the patients with PCOS had a 7.8-fold higher frequency of CYP1A1 Ile/Val genotype and a 7.4-fold higher frequency of CYP1A1 of any Val genotype (Ile/Val or Val/Val).WoSScopu

A Novel Missense Mutation of the Grk1 Gene in Oguchi Disease

Oguchi disease is a rare form of congenital stationary night blindness with an autosomal recessive inheritance pattern. The presence of S-antigen (SAG) and G-protein-dependent receptor kinase 1 (GRK1) mutations were investigated in the family members with Oguchi disease. All exons of the SAG and GRK1 genes were amplified by polymerase chain reaction and sequenced. The patients were shown to have characteristic clinical features of Oguchi disease. Gene analysis determined a novel GRK1 mutation c.923T>C, which caused Oguchi disease in all siblings. This mutation, was demonstrated by amino acid alignment analysis to be in a phylogenetically conserved region and resulted in an amino acid change from leucine to proline at position 308. Thus, the present study reports a novel missense mutation of GRK1 in the affected members of a consanguineous Turkish family. Homozygosity at position 308, which resides in the catalytic domain of the GRK1 gene, is the cause of Oguchi disease in this Turkish family.PubMedWoSScopu