Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'

In vitro micropropagation of almond (Amygdalus communis L. cv. Nonpareil)

An efficient in vitro propagation method was developed for almond (Amygdalus communis L. cv. Nonpareil). The effect of BA and kinetin (0.0, 0.5, 1.0, 2.0, 4.0 mgl-1) on the culture initiation of zygoticembryos isolated from mature seeds was investigated. A Murashige and Skoog (1962) (MS) medium containing 30 gl-1 sucrose, 0.5 and 1.0 mgl-1 N6-benzylaminopurine (BA) and 7 gl-1 agar resulted in amultiple shoot initiation at the rate of 11.0 ± 1.32 and 14.7 ± 2.12 shoot per explant, respectively, in 28 days of culture. The effects of a low concentration of BA (0.1, 0.5, 1.0 and 2.0 mgl-1) and differentcombinations of auxin + cytokinin were investigated for shoot proliferation. The best results for new shoot production were obtained from a MS culture medium which was supplemented with 1.0 mgl-1 BA.The rooting was achieved in a ½ MS medium supplemented with 8.0 mgl-1 indole acetic acid (IAA). The in vitro raised plants were acclimatized in a growth room and successfully transplanted to the field.This method here in described will be useful for the rapid multiplication of almond (A. communis L. cv. Nonpareil) in commercial exploitation