Israel Medical Association Journal

Background: Fetal ventriculomegaly is one of the more common fetal anomalies detected during prenatal screening.

Objectives: To assess the rate of genetic aberrations as the cause for ventriculomegaly in these fetuses.

Methods: A historic cohort study was conducted on 164 fetuses with sonographic diagnosis of ventriculomegaly. All cases were analyzed for karyotype and 41 cases were further analyzed by chromosomal microarray (CMA). The study group was subdivided by laterality, severity, and whether the ventriculomegaly was an isolated finding or not. Subgroups were compared and the study group was compared to a control group of 209 fetuses.

Results: Karyotype aberrations were more common among fetuses with ventriculomegaly (6.6%) compared to controls (0%, P < 0.001). CMA aberrations were more common in the non-isolated ventriculomegaly cases (24.1%) compared to controls (6.2%, P = 0.031). The rate of genetic aberrations was not associated with the degree of dilatation or laterality.

Conclusions: It is equivocal whether CMA testing should be conducted on every amniotic fluid sample taken from fetuses with isolated ventriculomegaly. However, if more anomalies are detected during an anatomical survey, CMA analysis should be conducted to decrease oversights of genetic diagnoses.

Background: Biallelic BLM gene mutation carriers are at an increased risk for cancer, including colorectal cancer (CRC). Whether heterozygous BLM gene mutations confer an increased cancer risk remains controversial.

Objectives: To evaluate CRC and endometrial cancer risk in BLM heterozygous mutation carriers.

Methods: Jewish Ashkenazim at high risk for colon or endometrial cancer and endometrial cancer cases unselected for family history were genotyped for the BLM^Ash predominant mutation.

Results: Overall, 243 high-risk individuals were included: 97 men CRC patients (55.12 ± 12.3 years at diagnosis), 109 women with CRC (56.5 ± 13.7 years), 32 women with endometrial cancer (58.25 ± 13.4 years) and 5 women with both CRC and endometrial cancer. In addition, 120 unselected Ashkenazi women with endometrial cancer (64.2 ± 11.58 years) were genotyped. The BLM^Ash mutation was present in 4/243 (1.65%) high-risk patients; 2 CRC (0.97%) 2 endometrial cancer (5.4%), and 1/120 unselected endometrial cancer patients (0.84%). Notably, in high-risk cases, BLM^Ash mutation carriers were diagnosed at a younger age (for CRC 47.5 ± 7.8 years; P = 0.32 ; endometrial cancer 49.5 ± 7.7 years; P = 0.36) compared with non-carriers.

Conclusions: Ashkenazi high risk CRC/endometrial cancer, and women with endometrial cancer have a higher rate of BLM^Ash heterozygous mutation compared with the general population. BLM^Ash heterozygous mutation carriers are diagnosed with CRC and endometrial cancer at a younger age compared with non-carriers. These observations should be validated and the possible clinical implications assessed.

Autoimmune diseases are classic examples of multifactorial disorders in which a large number of genes interact with environmental factors to form the final phenotype. Identification of the genes involved in these diseases is a daunting challenge. Initially the search involved the candidate approach where polymorphisms in suspected genes were tested for association in large cohorts of patients and controls. Today, the most widely used method is genome-wide association studies (GWAS), a method based on screening large panels of patients and controls with hundreds of thousands of single nucleotide polymorphisms (SNPs), with microarray-based technology. Unique families in which autoimmune diseases are caused by single genes are another alternative. The identification of candidate genes is often followed by studies that provide biologic plausibility for the findings. The widely expanding list of genes involved in autoimmune conditions show that the same genes frequently underlie the pathogenesis of different autoimmune diseases. Despite all available resources, the main void of heritability in autoimmune conditions is yet to be discovered. Identification of these genes will help define new biological pathways and identify novel targets for the development of new therapeutic drugs.