Long-term prospective clinical follow-up after BRCA1/2 presymptomatic testing: BRCA2 risks higher than in adjusted retrospective studies

The risks of breast cancer associated with gene faults in BRCA1 and BRCA2 have been reported to vary from as little as 30% (especially BRCA2) to as high as 90% by age 70 years. However, most studies that assessed risk look backwards at what has happened in families rather than forwards. These studies make adjustments […]

Read More…

High Risk of Tobacco-Related Cancers in CDKN2A Mutation-Positive Melanoma Families

In this study we have investigated cancer risks in members of Swedish melanoma-prone families with an inherited mutation in the tumor suppressor gene CDKN2A. We find significantly increased risks among carriers not only for melanoma but also for non-melanoma cancers, in particular pancreatic, lung, head and neck and gastro-esophageal cancers. We show a positive association […]

Read More…

A genome-wide association study of serum levels of prostate-specific antigen in the Japanese population

Prostate specific antigen (PSA) is a useful marker for screening of prostate cancer (PCa), one of the leading causes of death in the world. Here, we showed that two genetic variants in SLC45A3 and KLK3 genes are significantly associated with PSA levels in the Japanese population. The association of SLC45A3 was not known in Japanese. […]

Read More…

Pathogenic mutations in GLI2 cause a specific phenotype that is distinct from holoprosencephaly

Mutations in GLI2 have been associated with holoprosencephaly (HPE), a neuroanatomic anomaly resulting from incomplete cleavage of the developing forebrain, and an HPE-like phenotype involving pituitary anomalies and polydactyly. We collected the largest sample to date of individuals with variants affecting GLI2 and characterized their phenotype. This included previously published cases as well as new […]

Read More…

A missense mutation in the splicing factor gene DHX38 is associated with early-onset retinitis pigmentosa with macular coloboma

Retinitis pigmentosa is a group of genetically inherited eye diseases which represents the most frequent cause of inherited blindness worldwide. Persons with retinitis pigmentosa experience night blindness, which is followed by tunnel vision due to the progressive degeneration of the light sensing cells called rods and cones. Approximately 60 different genes can be defective in […]

Read More…

A familial disorder of altered DNA-methylation

Genomic imprinting is an epigenetic process leading to parent-of-origin specific DNA methylation and gene expression. There are several recognizable phenotypes caused by DNA-methylation changes at disease specific imprinted loci. In the recent years it became obvious that some patients exhibit changes of DNA-methylation at multiple imprinted loci. We report a family with three offspring who […]

Read More…

A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting > 30 million children worldwide. Children usually develop AIS around the time of the adolescent growth spurt, and girls are at greater risk of severe deformity requiring treatment. Until recently the causes of AIS have remained unknown. In 2011 a genome-wide association study (GWAS) […]

Read More…

ADAP2 in heart development: a candidate gene for the occurrence of Cardiovascular Malformations in NF1 Microdeletion Syndrome

The NF1 microdeletion syndrome is caused by the deletion of a chromosome 17 region encompassing the NF1 gene and flanking genes. We previously found that the patients with the syndrome display a significantly higher incidence of Cardiovascular Malformations (CVMs) than that observed in the NF1 patients with intragenic mutations, suggesting that genes present in the […]

Read More…

Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia

Sedaghatian-type spondylometaphyseal dysplasia is a rare syndrome characterized by abnormal bone development with shortened limbs and flattened spine.  Affected children also have heart rhythm defects and brain abnormalities such that they pass away shortly after birth.  Eighteen infants affected with this rare disease have been reported worldwide.  We studied two families and identified loss-of-function mutations […]

Read More…