Clinical features and health-related quality of life in adult patients with mucopolysaccharidosis IVA: the Spanish experience

Background: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults. The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL). Results: Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5–40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106–136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03–2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68–3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25–2.34) versus 2.25 (1.62–3.00) in patients not treated with ERT. Conclusions: The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams

Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome.

Two novel mutations of the ribosomal S6 kinase 2 gene (also known as RSK2) have been identified in two unrelated patients with Coffin-Lowry syndrome. The first mutation consists of a de novo insertion of a 5'-truncated LINE-1 element at position -8 of intron 3, which leads to a skipping of exon 4, leading to a shift of the reading frame and a premature stop codon. The L1 fragment (2800 bp) showed a rearrangement with a small deletion, a partial inversion of the ORF 2, flanked by short direct repeats which duplicate the acceptor splice site. However, cDNA analysis of the patient shows that both sites are apparently not functional. The second family showed the nucleotide change 803T>C in exon 10, resulting in the F268S mutation. This mutation was detected in two monozygotic twin patients and in their mother, who was mildly affected. The patients fulfill the clinical criteria of the syndrome, and therefore the mutation provides further support for the importance of phenylalanine at position 268, which is highly conserved in the protein kinase domain of many serine-threonine protein kinases

Changes in growth and soil microbial communities in reciprocal grafting clones between Populus deltoides males and females exposed to water deficit conditions

Key message. Our findings highlight that male-rooted clones (M/M and F/M) of Populus deltoides are more water-deficit tolerant than female-rooted clones (F/F and M/F), as shown by a smaller decrease in total biomass and net photosynthetic rate in the male-rooted clones. Context. It has been reported that graft clones (female scion and male rootstock) in poplars may be an option to mitigate the effects of water deficit on plants. However, the extent to which grafting mitigates the effect of soil water deficit on soil microorganisms remains poorly understood. Aims. The research was designed to investigate the effects of soil water deficit on plant growth, soil microbial communities, and soil enzymatic activities of the reciprocal graft clones of P. deltoides. Methods. Four different graft clones (female shoot scion and female rootstock, F/F; male shoot scion and female rootstock, M/F; male shoot scion and male rootstock scion, M/M; and female shoot scion and male rootstock, F/M) in P. deltoides were used. Two watering regimes, irrigation and soil water deficit (i.e., non-irrigation conditions, natural levels of precipitation) were included in the experiments. The microbial community structure was quantified using phospholipid fatty acid. Results. Under water deficit, the decreases in total biomass, net photosynthetic rates, and leaf nitrogen content were more evident in M/M and F/M than in F/F and M/F. Bacterial phospholipid fatty acids (PLFAs) and actinomycetal PLFAs remained unaffected in the four graft clones. In contrast, during soil water deficit, fungal PLFAs were higher in M/M and F/M soil coincided with higher extracellular activities of β-1,4-N-acetyl-glucosaminidase and leucine aminopeptidase. Conclusion. Male-rooted clones (M/M and F/M) are more tolerant to water deficit than female-rooted clones (F/F and M/F). It is possible that the better performance of M/M and F/M, when exposed to water deficit, is associated mainly with higher fine root activity, greater specific root length and root/shoot ratio as well as increased fungal PLFAs