Biomedical subjects

Jenny Morton

Publications and source records attributed to Jenny Morton.

5 recordsLinked to original sources

PubMed2006

Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene.

The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits food intake, and rodent models of BDNF disruption all exhibit increased food intake and obesity, as well as hyperactivity. We report an 8-year-old girl with hyperphagia and severe obesity, impaired cognitive function, and hyperactivity who harbored a de novo chromosomal inversion, 46,XX,inv(11)(p13p15.3), a region encompassing the BDNF gene. We have identified the proximal inversion breakpoint that lies 850 kb telomeric of the 5' end of the BDNF gene. The patient's genomic DNA was heterozygous for a common coding polymorphism in BDNF, but monoallelic expression was seen in peripheral lymphocytes. Serum concentration of BDNF protein was reduced compared with age- and BMI-matched subjects. Haploinsufficiency for BDNF was associated with increased ad libitum food intake, severe early-onset obesity, hyperactivity, and cognitive impairment. These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior.

Adult↗

PubMed2005

Ecstasy: pharmacology and neurotoxicity.

In part because it is amphetamine derived, ecstasy has inherited some of its parent compound's reputation for being neurotoxic. However, whereas amphetamine and methamphetamine undoubtedly cause irreversible brain damage with long-term use, the jury is still out on the party drug ecstasy. The deadly reputation of ecstasy has been fuelled by the tragic fates of healthy young clubbers who have died after taking the drug. However, compared with other recreational drugs, there have been very few ecstasy-related deaths. Further, there is little evidence for short-term neurotoxicity of ecstasy at recreational doses. That is not to say that ecstasy leaves the user neutral. Chronic ecstasy use causes depletion of serotonin, which has subtle but important long-term effects on cognition and mood. Although it seems unlikely that we will be faced with a generation of party goers who suffer from premature Parkinson's disease, so little is known about the long-term effects of ecstasy on mood, emotional states and cognitive function that at present we cannot predict what impact their use of ecstasy will have on the middle-age of the average ecstasy user.

Affect↗

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

Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux.

The homodimeric transmembrane receptor natriuretic peptide receptor B (NPR-B [also known as guanylate cyclase B, GC-B, and GUC2B]; gene name NPR2) produces cytoplasmic cyclic GMP from GTP on binding its extracellular ligand, C-type natriuretic peptide (CNP). CNP has previously been implicated in the regulation of skeletal growth in transgenic and knockout mice. The autosomal recessive skeletal dysplasia known as "acromesomelic dysplasia, type Maroteaux" (AMDM) maps to an interval that contains NPR2. We sequenced DNA from 21 families affected by AMDM and found 4 nonsense mutations, 4 frameshift mutations, 2 splice-site mutations, and 11 missense mutations. Molecular modeling was used to examine the putative protein change brought about by each missense mutation. Three missense mutations were tested in a functional assay and were found to have markedly deficient guanylyl cyclase activity. We also found that obligate carriers of NPR2 mutations have heights that are below the mean for matched controls. We conclude that, although NPR-B is expressed in a number of tissues, its major role is in the regulation of skeletal growth.

Abnormalities, Multiple↗

PubMed2003

An unusual family with multiple movement disorders.

Multiple movement disorders presenting in the same family are rare. We present an unusual family where generalized dystonia, Huntington's disease, progressive supranuclear palsy and secondary paroxysmal dyskinesia co-exist. The index case presented with young-onset dystonia and tested negative for the DYT1 gene deletion. Her father was similarly affected. The father's brother (paternal uncle of the index) also had abnormal movements-a mixture of chorea and dystonia-and tested positive for the HD expansion. His son had secondary paroxysmal dyskinesia, and tested negative for the HD expansion. The index case and her father were also negative for the HD expansion. A paternal aunt of two of the cases had a clinical diagnosis of progressive supranuclear palsy. Dystonia is known to be a genetically heterogeneous condition. The co-existence of inherited generalized dystonia with other movement disorders may provide clues to its genetic localization.

Adolescent↗