Opt-in for secondary findings as part of diagnostic whole-exome sequencing: Real-life experience from an international diagnostic laboratory.

Background: Discussion about the risks and benefits of offering secondary findings as part of genome-wide diagnostics lacks real-life data. We studied the opt-in decisions of patients/families referred to whole exome study (WES) in Blueprint Genetics (BpG), a genetic testing company with customers in over 70 countries to receive secondary findings. Based on the American College of Medical Genetics (ACMG) recommendations for reporting secondary findings, BpG offered testing of specific actionable genes without additional charge for specimens submitted to WES diagnostics.

Phenotype expansion and neurological manifestations of neurobehavioural disease caused by a variant in RFX7.

The RFX7 gene is one of eight genes within the regulatory factor X family. RFX7 is highly expressed in the brain and plays an important role in cell maturation and differentiation. It has only recently been implicated in disease in humans.

Infantile-Onset Charcot-Marie-Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a Gene Variant: A Case Report and Brief Review of the Literature.

Charcot-Marie-Tooth (CMT) is the most frequent group of inherited neuropathies and includes several heterogeneous phenotypes. Over 80 causative genes have been described so far. Variants in the microrchidia family CW-type zinc finger 2 () gene have been described in several axonal polyneuropathy (CMT2) patients with childhood or adult onset.

EGFR gene copy number predicts response to anti-EGFR treatment in RAS wild type and RAS/BRAF/PIK3CA wild type metastatic colorectal cancer.

Anti-EGFR antibodies are used for the treatment of RAS wild type metastatic colorectal cancer. We previously showed that EGFR gene copy number (GCN) predicts response to anti-EGFR therapy in KRAS exon 2 wild type metastatic colorectal cancer. The aim of our study was to analyse the predictive role of EGFR GCN in RAS/BRAF/PIK3CA wild type metastatic colorectal cancer.

Study of p53 gene mutations and placental expression in recurrent miscarriage cases.

This study aimed to investigate the role of p53 in early human development by screening patients with recurrent miscarriages (RM) for mutations in the p53 gene and by studying p53 expression in placental tissue. A total of 46 women with RM and 191 control women were included in the study. A sample was also obtained from 40 male partners of RM patients.

Do mitochondrial mutations cause recurrent miscarriage?

The cause of recurrent miscarriage (RM) can be identified in approximately 50% of cases, whereas in others, unknown genetic factors are actively being sought. As mitochondrial functions, and therefore also the mitochondrial genome [mitochondrial DNA (mtDNA)], have an important role in human development, through ATP production and participation in apoptosis, we aimed to study the role of mtDNA variations in RM. We screened 48 women with RM and 48 age-matched control women for heteroplasmic mitochondrial mutations using denaturing high performance liquid chromatography, a sensitive method that can detect approximately 5% heteroplasmy.

Non-synonymous sequence variants within the oxygen-dependent degradation domain of the HIF1A gene are not associated with pre-eclampsia in the Finnish population.

Background: Reduced placental perfusion predisposes to the maternal syndrome pre-eclampsia characterized by systemically reduced perfusion. Considerable data support the role of angiogenic factors in the development of the maternal syndrome. Hypoxia-inducible factor (HIF-1) mediates the cellular responses to hypoxia e.

Chorionic gonadotropin beta-gene variants are associated with recurrent miscarriage in two European populations.

Context: The incidence of recurrent miscarriage (RM) (>or=3 consecutive pregnancy losses) is estimated as 1-2% in fertile couples. Familial clustering of RM has suggested the contribution of a genetic component.

Objective: A low level of human chorionic gonadotropin (HCG) in maternal serum during the first trimester of the pregnancy is a clinically accepted risk factor for miscarriage.

Sex chromosome characteristics and recurrent miscarriage.

Objective: To investigate whether skewed X chromosome inactivation (XCI) and Y chromosome microdeletions are associated with recurrent miscarrige (RM).

Design: A retrospective study.

Setting: University hospital and genetic laboratory.

Variations of the Amnionless gene in recurrent spontaneous abortions.

Recurrent spontaneous abortions (RSA) are estimated to affect 0.5-1% of couples trying to have a child. The causes of RSA are unknown in the majority of cases.

Evaluation of RAD50 in familial breast cancer predisposition.

The genes predisposing to familial breast cancer are largely unknown, but 5 of the 6 known genes are involved in DNA damage repair. RAD50 is part of a highly conserved complex important in recognising, signalling and repairing DNA double-strand breaks. Recently, a truncating mutation in the RAD50 gene, 687delT, was identified in 2 Finnish breast cancer families.

Breast cancer patients with p53 Pro72 homozygous genotype have a poorer survival.

Purpose: The p53 R72P polymorphism has been suggested to play a role in many cancers, including breast cancer. Our aim was to evaluate association of R72P with breast cancer risk as well as histopathologic features of the breast tumors and survival.

Experimental Design: The germ line R72P genotype was defined among 939 Finnish familial and 888 unselected breast cancer patients and 736 healthy population controls.