Neurofibromatosis type 1: from genotype to phenotype

Although neurofibromatosis 1 (NF1) is a common genetic disorder, its expression is highly variable and unpredictable. Here, we review the genotype-phenotype correlations in NF1. Some NF1 patients with a given NF1 mutation may develop very severe disease while others with the same mutation have only mild symptoms, even in the same family. The clinical variability […]

Read More…

A systematic review of associated structural and chromosomal defects in oral clefts: when is prenatal genetic analysis indicated?

Oral clefts are being diagnosed prenatally more frequently. When informing future parents on outcome and prognosis, the category of cleft as well as the presence of other structural congenital anomalies is crucial. Especially the identification of an underlying chromosomal defect will influence prenatal counselling and management of the pregnancy significantly. To provide a basis for […]

Read More…

Clinical significance of copy number variations in the 11p15.5 imprinting control regions: new cases and review of the literature

The chromosomal region 11p15 harbours several imprinted genes, i.e. genes which are expressed in a parent-of-origin manner. Opposite molecular disturbances in 11p15 are associated with two distinct disorders associated with disturbed growth, Silver-Russell and Beckwith-Wiedemann syndrome. Due to the complexity of the 11p15 region and the interactions between the different genes, the interpretation of copy […]

Read More…

Identification of the first recurrent PAR1 deletion in Léri-Weill dyschondrosteosis and idiopathic short stature reveals the presence of a novel SHOX enhancer

SHOX, is a gene implicated in human growth.  Defects in SHOX, or its regulatory regions have been observed in ~60% of Léri-Weill dyschondrosteosis (LWD) patients, a skeletal dysplasia, and in 2-5% of idiopathic short stature (ISS) patients.  In this study, we identified the first recurrent deletion within the SHOX regulatory region in these disorders, 19/124 […]

Read More…

Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog

Holoprosencephaly is a common human brain malformation; there are many different known causes.  Sonic Hedgehog was the first gene in which mutations were found to cause holoprosencephaly .  Some individuals with Sonic Hedgehog mutations have very severe brain and facial malformations, and do not survive to be born.  However, some people have only subtle facial […]

Read More…

Translational Genomic Medicine: Common Metabolic Traits and Ancestral Components of Mexican Americans

Obesity, type 2 diabetes, hyperlipidaemia, hypertension and liver disease are common metabolic disorders in Mexican Americans, the largest minority population in the US. Mexican Americans are an admixed population with European, Amerindian and African ancestries. Ancestral analysis by genotyping a set of ancestry informative markers (AIMs) in this study identified associations between ancestral components and […]

Read More…

The immunogenetics of immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome

The immune system relies on a finely tuned balance between immunity to pathogens and cancers, and tolerance to healthy self, our environment and commensals. This equilibrium is dramatically disrupted in the Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. This rare disorder is caused by mutations in the FOXP3 gene, a master transcriptional regulator for the development […]

Read More…

Prostate cancer risk assessment model: a scoring model based on the Swedish Family-Cancer Database

Prostate cancer is the most common cancer in men and family history of cancer and age are the strongest contributing factors. We followed about 600,000 men from the Swedish Family-Cancer Database (world’s largest of its kind) for 10 years to design the Prostate Cancer Risk Assessment Model (PCRAM) for the first time, which enables clinicians […]

Read More…

Mutations in GRIP1 cause Fraser syndrome

Fraser syndrome (FS) is a rare genetically heterogeneous recessive disorder. FS patients are born with severe malformations affecting their eyes (cryptophthalmos), skin covering the digits (cutaneous syndactyly), respiratory tract, kidneys and genitals. The molecular defect underlying the majority of FS patients is unknown. Thus far mutations in two genes (FRAS1 and FREM2) are known to […]

Read More…