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 […]
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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 […]
Mutations in TUBB8 cause a multiplicity of phenotypes in human oocytes and early embryos
An essential feature of successful mammalian reproduction is the fusion of a sperm with a mature oocyte. We previously found that heterozygous mutations in TUBB8 caused oocyte maturation arrest. In this study, we identified novel heterozygous and homozygous mutations in TUBB8 that cause variability in the corresponding phenotypes of human oocytes and early embryos. For […]
Genes associated with common variable immunodeficiency: one diagnosis to rule them all?
Common variable immunodeficiency (CVID) is an immune disorder characterized by low antibody levels and an increased susceptibility to infections and immune-related complications. It is a heterogeneous disorder with a variable clinical presentation and severity. Thus far, single gene defects have been identified in about 2-10% of patients. As more disease genes are being identified, it […]
A Splicing Mutation in VPS4B Causes Dentin Dysplasia I
Dentin dysplasia I (DDI) is an autosomal dominant disorder characterized by rootless teeth with abnormal pulpal morphology. The etiology of DDI still remains largely unclear. Here, we identified VPS4B as a disease-causing gene for DDI by linkage analysis followed by deep sequencing of the candidate genes in a large Chinese family with DDI. A splicing mutation (IVS7+46C>G) […]