Browsing by Author "Khatami, Mehri"
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- Mitochondrial mutations in protein coding genes of respiratory chain including complexes IV, V, and MT-TRNA genes are associated risk factors for congenital heart diseasePublication . Heidari, Mohammad Mehdi; Khatami, Mehri; Kamalipour, Akram; Kalantari, Mustafa; Movahed, Mahsa; Emmamy, Mohammad Hayet; Hadadzadeh, Mehdi; Bragança, José; Namnabat, Mohsen; Mazrouei, BaharehMost studies aiming at unraveling the molecular events associated with cardiac congenital heart disease (CHD) have focused on the effect of mutations occurring in the nuclear genome. In recent years, a significant role has been attributed to mitochondria for correct heart development and maturation of cardiomyocytes. Moreover, numerous heart defects have been associated with nucleotide variations occurring in the mitochondrial genome, affecting mitochondrial functions and cardiac energy metabolism, including genes encoding for subunits of res-piratory chain complexes. Therefore, mutations in the mitochondrial genome may be a major cause of heart dis-ease, including CHD, and their identification and characterization can shed light on pathological mechanisms occurring during heart development. Here, we have analyzed mitochondrial genetic variants in previously re-ported mutational genome hotspots and the flanking regions of mt-ND1, mt-ND2, mt-COXI, mt-COXII, mt-ATPase8, mt-ATPase6, mt-COXIII, and mt-tRNAs (Ile, Gln, Met, Trp, Ala, Asn, Cys, Tyr, Ser, Asp, and Lys) en-coding genes by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) in 200 pa-tients with CHD, undergoing cardiac surgery. A total of 23 mitochondrial variations (5 missense mutations, 8 synonymous variations, and 10 nucleotide changes in tRNA encoding genes) were identified and included 16 novel variants. Additionally, we showed that intracellular ATP was significantly reduced (P=0.002) in CHD pa-tients compared with healthy controls, suggesting that the mutations have an impact on mitochondrial energy production. Functional and structural alterations caused by the mitochondrial nucleotide variations in the gene products were studied in-silico and predicted to convey a predisposing risk factor for CHD. Further studies are necessary to better understand the mechanisms by which the alterations identified in the present study contribute to the development of CHD in patients.
- Mutational and bioinformatics analysis of the NKX2.1 gene in a cohort of Iranian pediatric patients with congenital hypothyroidism (CH)Publication . Heidari, Mohammad Mehdi; Madani Manshadi, Seyed Ali; Eshghi, Ahmad Reza; Talebi, Fatemeh; Khatami, Mehri; Bragança, José; Ordooei, Mahtab; Chamani, Reyhane; Ghasemi, FarzanehCongenital hypothyroidism (CH) is the most common congenital endocrine disorder in neonates and children with a global incidence of 1 in 3,000–4,000. Adequate thyroid hormone levels in the bloodstream are essential for the normal growth and development of the nervous system in children. Consequently, CH is associated with irreversible central nervous system and mental health problems, as well as poor growth of untreated children with CH. Girls are more likely to be affected than boys (female to male ratios are 2:1) [1–3]. Early diagnosis methods for CH are still necessary to establish more efficient treatments of CH, which is an important public health issue worldwide, including developed countries [4]. CH can be classified either as primary or as central hypothyroidism, and it is an autosomal recessive disorder. But in a significant percentage of patients, CH is sporadic and non-hereditary and caused by de novo developmental defects in the thyroid gland (primary congenital hypothyroidism). Hereditary forms of CH with decreased thyroid hormone synthesis are either due to a defective thyroid gland development (thyroid dysgenesis) present in 80% of patients or to a failure in thyroid hormone synthesis (thyroid dyshormonogenesis) present in 20% of the patients [5, 6]. Thyroid dysgenesis (TD; OMIM 218700), which refers to the most common cause of congenital hypothyroidism and abnormal structural malformations in the thyroid, is subcategorized into: (i) thyroid ectopy, an abnormally located and small thyroid gland; (ii) thyroid athyreosis, complete lack of the thyroid gland in imaging studies; and (iii) hypoplasia, a smaller gland of thyroid tissue but in a normal position. Dyshormonogenesis (OMIM 274400–274900) refers to the failure of thyroid hormone synthesis by a structurally normal thyroid gland [7]. In recent years, the overall incidence of CH has increased, including the transient form of CH in children, which is a consequence of thyroid hormone deficiency due to low thyroxine and elevated thyrotropin expression. Temporary CH may show symptoms of mild dyshormonogenesis during the first months of life due to insufficient production of thyroxine (T4) [8, 9]. Transient CH usually resolves itself in the first few months of infancy because of an increase in thyroxine production, but some of these children may also be treated for CH in infancy with levothyroxine (a manufactured form of the thyroid hormone thyroxine). However, after treatment endogenous hormonal levels are normalized, and by the age of 3, these children no longer need medication.