• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1219-1224
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• 2015

Background: To date several common mutations in BRCA1 and BRCA2 associated with breast cancer have been reported in different populations. However, the common BRCA1 and BRCA2 mutations among breast cancer patients in Iran have not been described in detail. Materials and Methods: To comprehensively assess the frequency and distribution of the most common BRCA1 and BRCA2 mutations in Iranian breast cancer patients, we conducted this meta-analysis on 13 relevant published studies indentified in a literature search on PubMed and SID. Results: A total of 11 BRCA1 and BRCA2 distinct common mutations were identified, reported twice or more in the articles, of which 10 (c.2311T>C, c.3113A>G, c.4308T>C, c.4837A>G, c.2612C>T, c.3119G>A, c.3548A>G, c.5213G>A c.IVS16-92A/G, and c.IVS16-68A/G) mutations were in BRCA1, and 1 (c.4770A>G) was in BRCA2. The mutations were in exon 11, exon 13, intron 16, and exon 20 of BRCA1 and exon 11 of BRCA2. All have been previously reported in different populations. Conclusions: These meta analysis results should be helpful in understanding the possibility of any first true founder mutation of BRCA1/BRCA2 in the Iranian population. In addition, they will be of significance for diagnostic testing, genetic counseling and for epidemiological studies.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.19-24
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• 2016

Constitutional interstitial deletions of the long arm of chromosome 5 (5q) are quite rare, and the corresponding phenotype is not yet clearly delineated. Severe mental retardation has been described in most patients who present 5q deletions. Specifically, the interstitial deletion of chromosome 5q33.3q35.1, an extremely rare chromosomal aberration, is characterized by mental retardation, developmental delay, and facial dysmorphism. Although the severity of mental retardation varies across cases, it is the most common feature described in patients who present the 5q33.3q35.1 deletion. Here, we report a case of a de novo deletion of 5q33.3q35.1, 46,XY,del(5)(q33.3q35.1) in an 11-year-old boy with mental retardation; to the best of our knowledge this is the first case in Korea to be reported. He was diagnosed with severe mental retardation, developmental delay, facial dysmorphisms, dental anomalies, and epilepsy. Chromosomal microarray analysis using the comparative genomic hybridization array method revealed a 16-Mb-long deletion of 5q33. 3q35.1(156,409,412-172,584,708)x1. Understanding this deletion may help draw a rough phenotypic map of 5q and correlate the phenotypes with specific chromosomal regions. The 5q33.3q35.1 deletion is a rare condition; however, accurate diagnosis of the associated mental retardation is important to ensure proper genetic counseling and to guide patients as part of long-term management.

• Clinical and Experimental Reproductive Medicine
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• v.45 no.1
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• pp.48-51
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• 2018

We report the case of a 46-year-old Chinese male patient who visited our clinic complaining of infertility. Semen analysis revealed azoospermia, and azoospermia factor c region partial deletion (b1/b3) was detected using Y chromosome microdeletion analysis. Testicular sperm extraction was performed after genetic counseling. The bilateral ductus deferens and a portion of the epididymis were absent, whereas the remaining epididymis was expanded. Motile intratesticular spermatozoa were successfully extracted from the seminiferous tubule. On histopathology, nearly complete spermatogenesis was confirmed in almost every seminiferous tubule. To our knowledge, this is the first case report of b1/b3 deletion with a congenital bilateral absence of the vas deferens and almost normal spermatogenesis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.21 no.1
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• pp.74-80
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• 1999

A family is presented in which multiple odontogenic keratocysts have been expressed. 3 members of the two generations of family with features of multiple keratocysts, suspected basal cell nevus syndrome have been investigated. The proband, 19-year-old woman and her mother, and her brother suffered from these cysts and two female patients' disease have been recurred multiply though careful treatments. Close attention to the family and routine follow up will alert the clinician to its recurrences and genetic counseling and serial screening for the development of other symptoms, that is malignant skin carcinoma etc.

• BMB Reports
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• v.37 no.2
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• pp.246-253
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• 2004

Constitutional RB1 gene mutations were studied in a series of 21 families with unilateral and bilateral retinoblastoma patients. Peripheral blood lymphocytes were analyzed by "exon by exon" PCR-heteroduplex and sequencing. Mutations were identified in 6 (29%) of the patients. One mutation corresponded to an intronic polymorphism in g.174351T > A. The other five mutations resulted C to T exonic transitions, four were CGA sequences (g.65386, g.150037 in two patients, and g.162237), creating stop codons and presumably truncated proteins. The fifth one was new and resulted in alanine to valine substitution (g.73774). Two patients had the same the germline truncated mutation (g.150037C > T), one with a familial bilateral early onset retinoblastoma and one with a sporadic unilateral late onset retinoblastoma. The later type has not been previously described. This finding is discussed in the genotype/phenotype correlation context. Additionally, a single nucleotide change was found in six studied samples, where a C to T homozygous transversion was identified in intron 26 (IVS26 + 28). It is worthy the non concordance of the nucleotide with the published sequence. This analysis proved to be a useful method for the detection of mutations in the RB1 gene, and contributed to the adequate genetic counseling to patients and relatives.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.21-26
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• 2020

Purpose: To evaluate the additive value of prenatal chromosomal microarray analysis (CMA) in assessing increased nuchal translucency (NT) (≥3.5 mm) with normal karyotype and the possibility of detecting clinically significant genomic imbalance, based on specific indications. Materials and Methods: Invasive samples from 494 pregnancies with NT ≥3.5 mm, obtained from the Research Center of Fertility & Genetics of Hamchoon Women's Clinic between January 2019 and February 2020, were included in this study and CMA was performed in addition to a standard karyotype. Results: In total, 494 cases were subjected to both karyotype and CMA analyses. Among these, 199 cases of aneuploidy were excluded. CMA was performed on the remaining 295 cases (59.7%), which showed normal (231/295, 78.3%) or non-significant copy number variation (CNV), such as benign CNV or variants of uncertain clinical significance likely benign (53/295, 18.0%). Clinically significant CNVs were detected in 11 cases (11/295, 3.7%). Conclusion: Prenatal CMA resulted in a 3% to 4% higher CNV diagnosis rate in fetuses exhibiting increased NT (≥3.5 mm) without other ultrasound detected anomalies and normal karyotype. Therefore, we suggest using high resolution, non- targeting CMA to provide valuable additional information for prenatal diagnosis. Further, we recommend that a genetics specialist should be consulted to interpret the information appropriately and provide counseling and follow-up services after prenatal CMA.

• Journal of Genetic Medicine
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• v.15 no.2
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• pp.79-86
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• 2018

Purpose: This study aimed to evaluate the clinical usefulness of non-invasive prenatal testing (NIPT) as an alternative testing of invasive diagnostic testing in pregnancies with ultrasound abnormalities. Materials and Methods: This was a retrospective study of pregnant women with abnormal ultrasound findings before 24 weeks of gestation between April 2016 and March 2017. Abnormal ultrasound findings included isolated increased nuchal translucency, structural anomalies, and soft markers. The NIPT or diagnostic test was conducted and NIPT detected trisomy 21 (T21), T18, T13 and sex chromosomal abnormalities. We analyzed the false positive and residual risks of NIPT based on the ultrasound findings. Results: During the study period, 824 pregnant women had abnormal ultrasound findings. Among the study population, 139 patients (16.9%) underwent NIPT. When NIPT was solely performed in the patients with abnormal ultrasound findings, overall false positive risk was 2.2% and this study found residual risks of NIPT. However, the discordant results of NIPT differed according to the type of abnormal ultrasound findings. Discordant results were significant in the group with structural anomalies with 4.4% false positive rate. However, no discordant results were found in the group with single soft markers. Conclusion: This study found different efficacy of NIPT according to the ultrasound findings. The results emphasize the importance of individualized counseling for prenatal screening or diagnostic test based on the type of abnormal ultrasound.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.4
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• pp.310-316
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• 2020

Microarray technology represents a critical new advance in molecular cytogenetics. The development of this approach has provided fundamental insights into the molecular pathogenesis in clinical cytogenetics and has provided a clue to many unidentified or unexplained diseases. The approach allows a comprehensive investigation of thousands and millions of genomic loci simultaneously and enables the efficient detection of copy number alterations. The application of this technology has shown tremendous fluidity and complexity of the human genome, and has provided accurate diagnosis and appropriate clinical management in a timely and efficient manner for identifying genomic alterations. The clinical impact of the genomic alterations identified by microarrays is evolving into a diagnostic tool to identify high-risk patients better and predict patient outcomes from their genomic profiles. The transformation of conventional cytogenetics into an automated discipline will improve diagnostic yield significantly, leading to accurate diagnosis and genetic counseling. This article reviews cytogenetic technologies used to identify human chromosome alterations and highlights the potential utility of present and future genome microarray technology in the diagnosis.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.3
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• pp.192-199
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• 2023

Objective: This study was conducted to investigate chromosomal abnormalities and their correlations with clinical and radiological findings in females with primary amenorrhea (PA). Methods: Detailed forms were recorded for 470 females, including the construction of three-generation pedigrees. Peripheral venous blood was drawn, with informed consent, for cytogenetic analysis. Results: An abnormal karyotype was found in 16.38% of participants. The incidence of structural abnormalities (6.8%) exceeded that of numerical abnormalities (6.15%). Turner syndrome represented 45% of all numerical abnormalities. Furthermore, the Y chromosome was detected in 5% of females with PA. Among the structural chromosomal abnormalities detected (n=32) were mosaicism (25%), deletions (12.5%), isochromosomes (18.75%), fragile sites (3.12%), derivatives (3.12%), marker chromosomes (3.12%), and normal variants (29.125%). An examination of secondary sexual characteristics revealed that 29.6% of females had a complete absence of breast development, 29.78% lacked pubic hair, and 36.88% exhibited no axillary hair development. Radiological findings revealed that 51.22% of females had a hypoplastic uterus and 26.66% had a completely absent uterus. Abnormal ovarian development, such as the complete absence of both ovaries, absence of one ovary, one absent and other streak, or both streak ovaries, was observed in 69.47% of females with PA. Additionally 43.1%, 36.1%, 67.4%, and 8% of females had elevated levels of serum follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and prolactin, respectively. Conclusion: This study underscores the importance of karyotyping as a fundamental diagnostic tool for assessing PA. The cytogenetic correlation with these profiles will aid in genetic counseling and further management of the condition.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4513-4518
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• 2014

The prevalence of BRCA1 gene mutations in breast cancer differs between diverse ethnic groups. Relatively little information is known about patterns of BRCA1 mutations in early-onset breast cancer in women of Uighur or Han descent, the major ethnic populations of the Xinjiang region in China. The aim of this study was to identify BRCA1 mutations in Uighur and Han patients with early-onset (age <35 years), and sporadic breast cancer for genetic predisposition to breast cancer. For detection of BRCA1 mutations, we used a polymerase chain reaction single-stranded conformation polymorphism approach, followed by direct DNA sequencing in 22 Uighur and 13 Han women with early-onset sporadic breast cancer, and 32 women with benign breast diseases. The prevalence of BRCA1 mutations in this population was 22.9% (8/35) among early-onset sporadic breast cancer cases. Of these, 31.8% (7/22) of Uighur patients and 7.69% (1/13) of Han patients were found to have BRCA1 mutations. In 7 Uighur patients with BRCA1 mutations, there were 11 unique sequence alterations in the BRCA1 gene, including 4 clearly disease-associated mutations on exon 11 and 3 variants of uncertain clinical significance on exon 11, meanwhile 4 neutral variants on intron 20 or 2. None of the 11 BRCA1 mutations identified have been previously reported in the Breast Cancer Information Core database. These findings reflect the prevalence of BRCA1 mutations in Uighur women with early-onset and sporadic breast cancer, which will allow for provision of appropriate genetic counseling and treatment for Uighur patients in the Xinjiang region.