von Hippel-Lindau disease (vHL) is a hereditary tumor predisposition causing life-long risk of tumor development in multiple organs. In a national research project including all known vHL families in Denmark, we found that the survival of vHL patients has improved over the last 100 years, and is getting closer to that of their siblings without […]
Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations
Amelogenesis Imperfecta (AI) is a genetic condition characterized by tooth enamel quantitative or qualitative defects. The defects affect the enamel appearance, which can be chalky, discolored, thinner, pitted or grooved. Usually, a combination of different defects can be found within the same patient. In the last decade, studies have shown that AI may be associated […]
Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies
The gene POLR3B is associated with 4H leukodystrophy, a syndrome that includes reproductive failure (in the form of idiopathic hypogonadotropic hypogonadism (IHH)), neurologic disease (often in the form of ataxia), and hypodontia. To date, most patients reported to carry biallelic variants in POLR3B begin to show neurologic symptoms in early childhood, often before they are […]
New insights in the molecular signature of advanced medullary thyroid cancer: evidence of a bad outcome of cases with double RET mutations
Advanced sporadic MTC are characterized by a high prevalence of RET somatic mutations. In particular the M918T is the most frequent mutation but also small deletions/insertions (complex mutations can be present. In some cases more than one RET mutation can occur. K- or H-RAS mutations are also present even if at a lower frequency. RET […]
Reader’s letter: comments on “Salbutamol increases SMN mRNA and protein levels in spinal muscular atrophy cells”
Salbutamol increases SMN mRNA and protein levels in spinal muscular atrophy cells C Angelozzi, F Borgo, F D Tiziano, A Martella, G Neri, C Brahe J Med Genet 2008; 45: 29-31 eLetter ID: jmedgenet_el;2828 Article ID: 45/1/29 Article Date: 1 January 2008 http://jmg.bmj.com/content/early/2007/10/11/jmg.2007.051177 I just read the articles on SMA1, SMA2, SMA3. I felt it important to tell […]
The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease
Recessive mutations in the RMND1 gene, encoding the Required for Meiotic Nuclear Division protein 1, can cause defects in mitochondrial translation and oxidative phosphorylation, resulting in multi-system mitochondrial disease. In this multi-centre international study, we identified 14 new cases from 11 pedigrees with recessive RMND1 mutations including six novel, pathogenic variants. Hypotonia, developmental delay, congenital […]
De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy
Pathogenic variants in the X-linked KIAA2022 gene are known to cause severe intellectual disability in males. Until now, all reported related female carriers of these KIAA2022 disruptions were unaffected and only 3 affected female patients have been described so far. We now report 14 female patients with heterozygous de novo loss of function mutations of […]
Specifying the ovarian cancer risk threshold of ‘premenopausal risk-reducing salpingo-oophorectomy’ for ovarian cancer prevention: a cost-effectiveness analysis
Risk-reducing surgery to prevent ovarian cancer involves removal of tubes and ovaries. This has traditionally been performed in women at high risk (>1-in-10 chance) of getting ovarian cancer (e.g. BRCA1/BRCA2 carriers). However, the ovarian cancer risk level at which surgical prevention should be offered has not been previously defined. We undertook a health economic analysis […]
Identification of bi-allelicLRRK1mutations inosteosclerotic metaphyseal dysplasiaand evidence for locus heterogeneity
Osteosclerotic metaphyseal dysplasia is a unique form of osteopetrosis characterized by dysplasiaof metaphyses of tubular bones with increased bone density. By exome sequencing, we found a homozygous mutation, c.5938_5944del[p.E1980Afs*66]in LRRK1 (Leucin-rich repeat kinase 1). LRRK1 was highly expressed in differentiated osteoclast. The patient’s phenotype was very similar to that of Lrrk1 knockout mice that we […]
Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head
Osteonecrosis of the femoral head is a painful and debilitating bone disease that causes bone death at the hip leading to its collapse and subsequent end-stage osteoarthritis. The disease is poorly understood limiting treatment options to invasive surgical procedures such as total hip replacement. We have identified a Canadian family of Greek origin with osteonecrosis […]