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As the most common type of inherited retinal degenerative disease, retinitis pigmentosa (RP) has taken clinical and prenatal attention. Considering the clinical importance of consanguineous marriages, new mutations in this type of pregnancy have a high risk and increase the importance of Prenatal Diagnosis (PND). In vitro analysis was done through Whole Exome Sequencing (WES) for a 36-year-old woman who was referred to a genetic laboratory in Kermanshah in 2021 for PND. The woman had consanguineous marriage and was pregnant with twins (a boy and a girl). Mutation confirmation tests were also performed on her husband and both fetuses to find mutations. Moreover, in silico analyses were performed by SWISS-MODEL, ProSA, Molprobity, Swiss-Pdb Viewer, and ERRAT. The WES analysis showed a novel mutation of the RP2 gene (exon2:c. 359G>C: p.R120P) in the 36-year-old pregnant woman. Mutations identified in her husband and her twins revealed changes in protein conformations. Further modeling and validation evaluations showed the replacement of Arg by Pro at the 120th residue site of the cognate protein. For the first time, our report introduced a novel missense mutation in the RP2 gene associated with severe signs of RP in an Iranian family based on an X-linked recessive pattern of genetic inheritance. These findings may pave the way for a better diagnosis of RP in genetic counseling and PND. [ABSTRACT FROM AUTHOR]

Congenital Fibrosis of the Extra Ocular Muscles1 (CFEOM1) is an autosomal dominant condition, caused by mutation in the KIF21A and TUBB3. It is characterized by congenital non-progressive restrictive ophthalmoplegia and ptosis. Mutational analysis of the known genes in such rare diseases by Sanger sequencing not only prevents wasting the time and expenses but also speeds diagnosis process, genetic counseling, and the possibility of prenatal diagnosis. Here, for the first time, association of pathogenic variant c.2860C>T in KIF21A gene in an Iranian family with positive history of CFEOM1A was reported. [ABSTRACT FROM AUTHOR]

The major defect in α-thalassemia (α-thal) is a single or double gene deletion. The aim of this study was to evaluate the α-thal mutations in two provinces of Southern Iran, Fars & Kohkeloye and Bouyer Ahmad. A total of 2000 subjects with microcytic hypochromic anemia was selected as a study group; finally, 1177 subjects were found to be α-thal mutation carriers by gap-polymerase chain reaction (gap-PCR) protocols and were confirmed by multiplex PCR and reverse hybridization test strips. A total of 1195 mutated α-globin alleles was identified in these patients that includes at least 10 different gene mutations. The most common mutation found was -α3.7 (rightward deletion) (71.7%%) and α−5 nt (IVS-I, -TGAGG) and the polyadenylation signal site (poly A1; AATAA A>AATAA G) were the second and third most common mutations (7.0 and 4.2%%, respectively). In countries like Iran, with a high prevalence of thalassemia, identifying different mutations is helpful in carrier screening, genetic counseling and prenatal diagnosis of at-risk couples for the prevention of the birth of babies affected by severe thalassemic anomalies. [ABSTRACT FROM AUTHOR]

Abstract: In Iran, the prevalence of beta-thalassemia trait is approximately 4–8% in most areas, and in Mazandaran province 10% of the population are carriers. Twenty four beta-globin gene mutations were identified in 1635 persons with beta-thalassemia trait using reverse dot blot and restriction fragment length polymorphism analysis. The predominant mutations included IVSII-1 (G-A) (61%), codon 30 (G-C) (7.5%), codon 22 (−7bp) (6.2%), codon 8 (−AA) (5.4%) and IVSI-5 (G-C) (3.6%). These mutations were in different haplotypes, with IVSII-1 being the most heterogeneous. Other less frequent mutations included IVS-II-745 (C-G), codon 44 (−C), codon 39 (C-T), codon 5 (−CT), IVS I-110 (G-A), IVSI-130 (G-C), Fr8/9 (+G), IVSI-1 (G-A), and IVSI (−25bp). All rare mutations except IVSI-130 were encountered in a unique haplotype. The diversity of these mutations reflects the historical admixture of genes in the region. The high prevalence of IVSII-1 (G-A) compared to other parts of the country and the world suggests a founder effect. Our data provide a basis for genetic counseling and prenatal diagnosis. [Copyright &y& Elsevier]