Identification of Two Novel Mutations in the <i>ATM</i> Gene from Patients with Ataxia-Telangiectasia by Whole Exome Sequencing

Heidari, Masoud; Soleyman-Nejad, Morteza; Taskhiri, Mohammad Hossein; Shahpouri, Javad; Isazadeh, Alireza; Ahangari, Roghayyeh; Mohamadi, Ali Reza; Ebrahimi, Masoumeh; Karimi, Hadi; Bolhassani, Manzar; Karimi, Zahra; Heidari, Mansour

doi:10.2174/1389202920666191107153734

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…The products of PCR were sequenced using ABI 3130 automated sequencer (Applied Biosystems, Forster City, CA, USA). The obtained sequences were analyzed using Mutation Surveyor software 19 …”

Section: Methodsmentioning

confidence: 99%

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Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Khorrami

Goleij

Karamad

et al. 2021

Clinical Laboratory Analysis

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Background Merosin‐deficient congenital muscular dystrophy type 1A (MDC1A) is occurred by mutations in LAMA2 gene that encodes the laminin α2 chain (merosin). MDC1A is a predominant subtype of congenital muscular dystrophy. Herein, we identified two missense mutations in LAMA2 gene in compound heterozygous status in an Iranian patient with MDC1A using whole‐exome sequencing (WES). Methods In the present study, we evaluated genetic alterations in an Iranian 35‐month‐old boy with MDC1A and his healthy family using WES method. The identified mutations further confirmed by Sanger sequencing method. Finally, in silico analysis was conducted to further evaluation of molecular function of the identified genetic variants. Results We identified two potentially pathogenic missense mutations in compound heterozygous state (c.7681G>A p.Gly2561Ser and c.4840A>G p.Asn1614Asp) in LAMA2 gene as contributing to the MDC1A phenotype. The healthy parents of our proband are single heterozygous for identified mutations. These variants were found to be pathogenic by in silico analysis. Conclusions In general, we successfully identified LAMA2 gene mutations in an Iranian patient with MDC1A using WES. The identified mutations in LAMA2 gene can be useful in genetic counseling, prenatal diagnosis, and predicting prognosis of MDC1A.

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Section: Methodsmentioning

confidence: 99%

“…The capture library was sequenced via 2×150 paired‐end sequencing on a Hiseq2000 Sequencer (Illumina, United States). 17 …”

Section: Methodsmentioning

confidence: 99%

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Khorrami

Goleij

Karamad

et al. 2021

Clinical Laboratory Analysis

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“…The most common manifestations of this disease in infants are a history of oligohydramnios enlargement of kidneys and pulmonary hypoplasia. Moreover, other organs besides the kidney are also involved in patients with PKD [ 4 , 7 ]. Although the relationship between genotype and phenotype in this disease is not fully understood, the presence of truncating mutations usually results in a severe form of disease and death in the fetus [ 4 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Two Novel Mutations in PKHD1 Gene from Two Families with Polycystic Kidney Disease by Whole Exome Sequencing

Heidari

Gharshasbi

Isazadeh

et al. 2021

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Background:: Polycystic kidney disease (PKD) is an autosomal recessive disorder resulting from mutations in the PKHD1 gene on chromosome 6 (6p12), a large gene spanning 470 kb of genomic DNA. Objective: The aim of the present study was to report newly identified mutations in the PKHD1 gene in two Iranian families with PKD. Materials and Methods: Genetic alterations of a 3-month-old boy and a 27-year-old girl with PKD were evaluated using whole-exome sequencing. The PCR direct sequencing was performed to analyse the co-segregation of the variants with the disease in the family. Finally, the molecular function of the identified novel mutations was evaluated by in silico study. Results: In the 3 month-old boy, a novel homozygous frameshift mutation was detected in the PKHD1 gene, which can cause PKD. Moreover, we identified three novel heterozygous missense mutations in ATIC, VPS13B, and TP53RK genes. In the 27-year-old woman, with two recurrent abortions history and two infant mortalities at early weeks due to metabolic and/or renal disease, we detected a novel missense mutation on PKHD1 gene and a novel mutation in ETFDH gene. Conclusion: In general, we have identified two novel mutations in the PKHD1 gene. These molecular findings can help accurately correlate genotype and phenotype in families with such disease in order to reduce patient births through preoperative genetic diagnosis or better management of disorders.

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“…3 Polymerase chain reaction (PCR) based techniques are used for the diagnosis of specific genetic mutations of embryos. 4 Chromosomal screening of trophectoderm (TE) biopsies of blastocysts assesses the development of the euploid embryo.…”

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confidence: 99%

“…Biopsy for preimplantation genetic diagnosis (PGT-M) can be applied at different stages of embryonic development: zygotes (polar body biopsy), cleavage stage (blastomere biopsy), or blastocysts (trophectoderm biopsy) . Polymerase chain reaction (PCR) based techniques are used for the diagnosis of specific genetic mutations of embryos …”

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Noninvasive Pregestational Genetic Testing of Embryos Using Smart Sensors Array

et al. 2022

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Pregestational genetic testing of embryos is the conventional tool in detecting genetic disorders (fetal aneuploidy and monogenic disorders) for in vitro fertilization (IVF) procedures. The accepted clinical practice for genetic testing still depends on biopsy, which has the potential to harm the embryo. Noninvasive genetic prenatal testing has not yet been achieved. In this study, embryos with common genetic disorders created through IVF were tested with an artificially intelligent nanosensor array. Volatile organic compounds emitted by the culture fluid of embryos were analyzed with chemical gas sensors. The obtained results showed significant discrimination between the embryos with different genetic diseases and their wild-types. Embryos were obtained from the same clinical center for avoiding differences based on clinical and demographical characteristics. The achieved discrimination accuracy was 81% for PKD disease, 90% for FRAX disease, 85% for HOCM disease, 90% for BRCA disease, and 100% for HSCR disease. These proof-of-concept findings might launch the development of a noninvasive approach for early assessment of embryos by examining the culture fluid of the embryos, potentially enabling noninvasive diagnosis and screening of genetic diseases for IVF.

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Identification of Two Novel Mutations in the ATM Gene from Patients with Ataxia-Telangiectasia by Whole Exome Sequencing

Cited by 6 publications

References 23 publications

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Identification of Two Novel Mutations in PKHD1 Gene from Two Families with Polycystic Kidney Disease by Whole Exome Sequencing

Noninvasive Pregestational Genetic Testing of Embryos Using Smart Sensors Array

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