Fatal hyperammonaemia due to late-onset ornithine transcarbamylase deficiency

In this case report we describe a 67-year-old male, admitted to the ICU with pneumonia who unexpectedly developed a fatal coma due to hyperammonaemia. At postmortem the diagnosis late-onset ornithine transcarbamylase deficiency was made. The non-specific clinical presentation, the rapid deterioration and incidentally the fatal outcome all underline the importance of recognition and knowledge of this genetic disorder. Several measures to treat and prevent potentially fatal episodes of hyperammonaemia are available, if only the disorder is recognised in time. In retrospect, several clues to the diagnosis were available in this fatal case, such as voluntary protein avoidance, as well as several male family members who died at a young age of an unknown cause. After his death, two daughters were discovered to be carriers of an OTC gene mutation, as well as his infant grandson. We emphasise the importance of obtaining ammonia levels in all patients with unexplained coma, seizures or cerebral oedema, irrespective of their age, especially in patients in the ICU or in an otherwise catabolic state

De novo recurrent germline mutation of the BRCA2 gene in a patient with early onset breast cancer

Germline mutations in either of the two major breast cancer predisposition genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast/ovarian cancer. Identification of breast cancer patients carrying mutations of these genes is primarily based on a positive family history of breast/ovarian cancer or early onset of the disease or both. In the course of mutation screening of the BRCA1 and BRCA2 genes in a hospital based series of patients with risk factors for hereditary breast/ovarian cancer, we identified a germline mutation in the BRCA2 gene (3034del4) in a patient with early onset breast cancer and no strong family history of the disease. Subsequent molecular analysis in her parents showed that neither of them carried the mutation. Paternity was confirmed using a set of highly polymorphic markers, showing that the proband carried a de novo germline mutation in the BRCA2 gene. Interestingly, 3034del4 is a recurrent mutation occurring in a putative mutation prone region of the BRCA2 gene. Our study presents the first case in which a de novo germline mutation in the BRCA2 gene has been identified, and supports previous results of haplotype studies, confirming that the 3034del4 mutation has multiple independent origins.


Keywords: breast cancer; BRCA2 gene; de novo mutatio

Neurofibromatosis presenting with a cherubism phenotype.

Item does not contain fulltextWe report on a child who presented clinical manifestations of both neurofibromatosis type 1 (NF1) and cherubism. With genetic testing, we found a mutation in the NF-1 gene, confirming the neurocutaneous disorder. Histology when correlated with radiological evaluation of a mandibular biopsy was consistent with cherubism. This is the first report in the literature of a child with proven neurofibromatosis type 1 and cherubism without extragnathic lesions. This emphasises that cherubism is a clinical phenotype that can be associated with a number of germline mutations involving SH3BP2, PTPN11 and NF1