We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy.
A previously undescribed pollination system involving a monoecious tree species, Artocarpus integer (Moraceae), pollinator gall midges, and fungi is reported from a mixed dipterocarp forest in Sarawak, Borneo. The fungus Choanephora sp. (Choanephoraceae, Mucorales, Zygomycetes) infects male inflorescences of A. integer, and gall midges (Contarinia spp., Cecidomyiinae, Diptera) feed on the fungal mycelia and oviposit on the inflorescence. Their larvae also feed on the mycelia and pupate in the inflorescence. The gall midges are also attracted by female inflorescences lacking mycelia, probably due to a floral fragrance similar to that of male inflorescences. Because of the sticky pollen, dominance of Contarinia spp. in flower visitors, and pollen load observed on Contarinia spp. collected on both male and female inflorescences, Artocarpus integer is thought to be pollinated by the gall midges. Although several pathogenic fungi have been reported to have interactions with pollinators, this is the first report on a pollination mutualism in which a fungus plays an indispensable role. The pollination system described here suggests that we should be more aware of the roles fungi can play in pollinations.
The pollinators of 29 ginger species representing 11 genera in relation to certain floral morphological characteristics in a mixed-dipterocarp forest in Borneo were investigated. Among the 29 species studied, eight were pollinated by spiderhunters (Nectariniidae), 11 by medium-sized Amegilla bees (Anthophoridae), and ten by small halictid bees. These pollination guilds found in gingers in Sarawak are comparable to the pollination guilds of neotropical Zingiberales, i.e., hummingbird-, and euglossine-bee-pollinated guilds. Canonical discriminant analysis revealed that there were significant correlations between floral morphology and pollination guilds and suggests the importance of plant-pollinator interactions in the evolution of floral morphology. Most species in the three guilds were separated on the plot by the first and second canonical variables. Spiderhunter-pollinated flowers had longer floral tubes, while Amegilla-pollinated flowers had wider lips than the others, which function as a platform for the pollinators. Pistils and stamens of halictid-pollinated flowers were smaller than the others. The fact that gingers with diverse morphologies in a forest with high species diversity were grouped into only three pollination guilds and that the pollinators themselves showed low species diversity suggests that many species of rare understory plants have evolved without segregating pollinators in each pollination guild.
Pollination ecology of an emergent tree species, Shorea (section Mutica) parvifolia (Dipterocarpaceae), was studied using the canopy observation system in a lowland dipterocarp forest in Sarawak, Malaysia, during a general flowering period in 1996. Although the species has been reported to be pollinated by thrips in Peninsular Malaysia, our observations of flower visitors and pollination experiments indicated that beetles (Chrysomelidae and Curculionidae, Coleoptera) contributed to pollination of S. parvifolia in Sarawak. Beetles accounted for 74% of the flower visitors collected by net-sweeping, and 30% of the beetles carried pollen, while thrips accounted for 16% of the visitors, and 12% of the thrips carried pollen. The apical parts of the petals and pollen served as a reward for the beetles. Thrips stayed inside the flower almost continuously after arrival, and movements among flowers were rare. Fruit set was significantly increased by introduction of beetles to bagged flowers, but not by introduction of thrips. Hand-pollination experiments and comparison of fruit set in untreated, bagged, and open flowers suggested that S. parvifolia was mainly outbreeding.
Flowerings and flower visitors were observed continuously in alowland dipterocarp forest in Sarawak, Malaysia, for 53 mo in1992-1996. Flower visitors of 270 plant species were observed orcollected, and pollinators were assessed by observing body contact tostigmas and anthers. We recognized 12 categories of pollination systems.Among them, plants pollinated by social bees included the largest numberof species (32%) and were followed by beetle-pollinated species(20%). Pollination systems were significantly related with somefloral characters (flowering time of day, reward, and floral shape), butnot with floral color. Based on the relationships between pollinatorsand floral characters, we described pollination syndromes found in alowland dipterocarp forest. The dominance of social bees and beetlesamong pollinators is discussed in relation to the general floweringobserved in dipterocarp forests of West Malesia. In spite of high plantspecies diversity and consequent low population densities of lowlanddipterocarp forests, long-distance-specific pollinators were uncommoncompared with theNeotropics.
Neurology. 2010 Jul 6;75(1):64-71
OBJECTIVE: To describe the current treatment; clinical, biochemical, and molecular findings; and clinical follow-up of patients with aromatic l-amino acid decarboxylase (AADC) deficiency.
METHOD: Clinical and biochemical data of 78 patients with AADC deficiency were tabulated in a database of pediatric neurotransmitter disorders (JAKE). A total of 46 patients have been previously reported; 32 patients are described for the first time.
RESULTS: In 96% of AADC-deficient patients, symptoms (hypotonia 95%, oculogyric crises 86%, and developmental retardation 63%) became clinically evident during infancy or childhood. Laboratory diagnosis is based on typical CSF markers (low homovanillic acid, 5-hydroxyindoleacidic acid, and 3-methoxy-4-hydroxyphenolglycole, and elevated 3-O-methyl-l-dopa, l-dopa, and 5-hydroxytryptophan), absent plasma AADC activity, or elevated urinary vanillactic acid. A total of 24 mutations in the DDC gene were detected in 49 patients (8 reported for the first time: p.L38P, p.Y79C, p.A110Q, p.G123R, p.I42fs, c.876G>A, p.R412W, p.I433fs) with IVS6+ 4A>T being the most common one (allele frequency 45%).
CONCLUSION: Based on clinical symptoms, CSF neurotransmitters profile is highly indicative for the diagnosis of aromatic l-amino acid decarboxylase deficiency. Treatment options are limited, in many cases not beneficial, and prognosis is uncertain. Only 15 patients with a relatively mild form clearly improved on a combined therapy with pyridoxine (B6)/pyridoxal phosphate, dopamine agonists, and monoamine oxidase B inhibitors.