Novel Mutation in LARP7 in Two Iranian Consanguineous Families with Syndromic Intellectual Disability and Facial Dysmorphism.

BACKGROUND: Recently, we have reported mutations in LARP7 gene, leading to neurodevelopmental disorders (NDDs), the most frequent cause of disability in children with a broad phenotype spectrum and diverse genetic landscape. METHODS: Here, we present two Iranian patients from consanguineous families with syndromic intellectual disability, facial dysmorphism, and short stature. RESULTS: Whole-exome sequencing (WES) revealed a novel homozygous stop-gain (c.C925T, p.R309X) variant and a previously known homozygous acceptor splice-site (c.1669-1_1671del) variant in LARP7 gene, indicating the diagnosis of Alazami syndrome. CONCLUSION: These identified variants in patients with Alazami syndrome were consistent with previously reported loss of function variants in LARP7 and provide further evidence that loss of function of LARP7 is the disease mechanism.

Correlation between important genes of mTOR pathway (PI3K and KIT) in Iranian women with sporadic breast cancer.

Background: PI3K/Akt/mTOR pathway is a crucial pathway in the angiogenesis, tumour growth and cell differentiation of several cancers. The PI3K and KIT genes are key genes of this pathway. Previous studies have reported the importance of these genes in the development of gastrointestinal carcinoma, leukaemia, and melanomas. The role of mutations and overexpression of PI3K and KIT genes in breast cancer has been previously proved. This study investigates the correlation between PI3K and KIT gene mutations in sporadic breast cancer. Methods: Multiplex Ligation-dependent Probe Amplification (MLPA) technique was used to determine the Copy Number Variation (CNV) of PI3K and KIT genes in 34 breast cancer tumours and PCR-sequencing was used to detect the mutation in PI3K exons 9 and 20. Results: Our results reported that 27% of patients had CNV of the KIT gene; whereas, 20% and 17.5% of patients, had mutation and CNV in the PI3K gene, respectively. We did not found a significant correlation between the mutations of PI3K and KIT genes. Conclusion: About two-tenth of the patients revealed CNV and lesser than two-tenth indicated mutation in the PI3K gene, whereas one-third of the patients demonstrated CNV in the KIT gene. Thus, administration of the PI3K and KIT gene inhibitor drugs might be proposed to suppress breast cancer in patients with mutation and CNV of each of these individual genes.

Relationship Between PIK3CA Amplification and P110α and CD34 Tissue Expression as Angiogenesis Markers in Iranian Women with Sporadic Breast Cancer.

BACKGROUND AND OBJECTIVE: The PI3K/AKT/mTOR pathway is known to play an important role in regulating angiogenesis both in normal and breast cancer (BC) tissues. PIK3CA amplification was reported in various malignancies, including approximately 10% of BC cases. The aim of this study was to identify the frequency of PIK3CA amplification in Iranian female patients suffering from BC. Additionally, possible association between PIK3CA amplification and P110α expression with microvascular density (MVD) was examined. METHODS: DNA samples were extracted from paraffin embedded tumor tissue blocks and copy number changes were evaluated by MLPA Technique. The results were analyzed by coffalyzer software. The tissue expression of P110α and CD34 was assessed using immunohistochemistry. RESULTS: Ten out of 40 samples (17.5%) showed amplification in PIK3CA gene and 22 out of 40 samples (55%) showed overexpression in P110α. For CD34, from 40 samples, 20 (50%), 15 (37.5%) and 5 (12.5%) had scores 1+, 2+ and 3+, respectively. CONCLUSION: No significant association was detected between gain of PIK3CA copy number and P110α or CD34 tissue expression.

Mutation Screening of BRCA Genes in 10 Iranian Males with Breast Cancer.

Male breast cancer is a rare disease with an increasing trend. Due to limited information especially about the genetic basis of the disease in Iran and the lower age of its onset, the disease requires more attention. The aim of this study was to screen the male patients with breast cancer for BRCA mutations as well as tissue markers of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER-2) and cytokeratin 5/6 (CK5/6). Ten Iranian males with breast cancer were selected regardless of their histologic subtypes, age and family history from patients referred to Mehrad, Day and Parsian hospitals in Tehran, Iran, during a two-year period. Paraffin blocks of the tumoral regions were tested for ER, PR, HER-2 and CK5/6 immunostaining. DNA extraction was carried out on the EDTA blood samples followed by Sanger sequencing. Immunohistochemistry results for ER, and PR were negative in 2 out of 10 patients, while the results of HER-2 and CK5/6 were negative in all the cases. A missense mutation in exon 18 of BRCA1 and a nonsense mutation in exon 25 of in BRCA2 were detected in one patient each. Both patients belonged to luminal A subtype. Despite the low number of patients in this study, it could be concluded that mutations in BRCA1 and BRCA2 occur in male breast cancer patients of luminal A subtype. The negative status of the tissue markers could not be used for the prediction of BRCA mutations.