Biomedical subjects

Elisabeth Rosser

Publications and source records attributed to Elisabeth Rosser.

4 recordsLinked to original sources

PubMed2006

Frameshift mutation in GJA12 leading to nystagmus, spastic ataxia and CNS dys-/demyelination.

Mutations in GJA12 have been shown to cause Pelizaeus-Merzbacher-like disease (PMLD). We present two additional patients from one family carrying a homozygous frameshift mutation in GJA12. Both presented initially with nystagmus. The older girl developed ataxia first, then progressive spastic ataxia. The younger boy suffered from severe sensory neuropathy. Magnetic resonance imaging (MRI) of both children showed progressive demyelination in addition to dysmyelination, and also characteristic brainstem abnormalities. In children with nystagmus, ataxia and dysmyelination, mutation analysis of GJA12 should be considered early, especially if inheritance is autosomal recessive.

Ataxia↗

PubMed2006

Mutation in Rab3 GTPase-activating protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf syndrome.

We identified a homozygous missense mutation in the noncatalytic subunit (RAB3GAP2) of RAB3GAP that results in abnormal splicing in a family with congenital cataracts, hypogonadism, and mild mental retardation (Martsolf syndrome). Recently, mutations in the catalytic subunit of RAB3GAP (RAB3GAP1), a key regulator of calcium-mediated hormone and neurotransmitter exocytosis, were reported in Warburg micro syndrome, a severe neurodevelopmental condition with overlapping clinical features. RAB3GAP is a heterodimeric protein that consists of a catalytic subunit and a noncatalytic subunit encoded by RAB3GAP1 and RAB3GAP2, respectively. We performed messenger RNA-expression studies of RAB3GAP1 and RAB3GAP2 orthologues in Danio rerio embryos and demonstrated that, whereas developmental expression of rab3gap1 was generalized (similar to that reported elsewhere in mice), rab3gap2 expression was restricted to the central nervous system. These findings are consistent with RAB3GAP2 having a key role in neurodevelopment and may indicate that Warburg micro and Martsolf syndromes represent a spectrum of disorders. However, we did not detect RAB3GAP2 mutations in patients with Warburg micro syndrome. These findings suggest that RAB3GAP dysregulation may result in a spectrum of phenotypes that range from Warburg micro syndrome to Martsolf syndrome.

Abnormalities, Multiple↗

PubMed2005

Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome.

Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of the Rab3 pathway implicated in exocytic release of neurotransmitters and hormones, in 12 families with Micro syndrome. We hypothesize that the underlying pathogenesis of Micro syndrome is a failure of exocytic release of ocular and neurodevelopmental trophic factors.

Catalytic Domain↗

PubMed2004

Inherited cancer in children: practical/ethical problems and challenges.

Over recent years significant molecular advances have led to a better understanding of the genetics of both syndromic and non-syndromic paediatric cancers. In addition many hereditary cancer predisposition syndromes are now recognised, some of which have implications for children in affected families. Improvements in gene mutation screening will increase the sensitivity, accuracy and therefore the applicability of genetic testing in these conditions. This review will deal with four main areas pertaining to paediatric cancer genetics (i) genetic aspects of some non-syndromic paediatric cancers (ii) paediatric cancer predisposition syndromes, (iii) the management of children in families with predominantly adult- onset cancer predisposition syndromes and (iv) special ethical, legal, social and psychological considerations in the management of children, with actual or possible genetic cancer predisposition. Current concepts and controversies in the rapidly changing field of paediatric cancer genetics will be examined in detail and the application of existing guidelines and their limitations will be discussed.

Child↗