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APOE genotype is the strongest genetic risk factor for Alzheimer’s Disease (AD). The low degree of homology between mouse and human APOE is a concerning issue in preclinical models currently used to study the role of this gene in AD pathophysiology. A key objective of ADAPTED (Alzheimer’s Disease Apolipoprotein Pathology for Treatment Elucidation and Development) project was to generate in vitro models that better recapitulate human APOE biology. We describe a new set of induced pluripotent stem cells (iPSC) lines carrying common APOE variants (Ɛ2, Ɛ3, and Ɛ3/Ɛ4) and a knock-out isogenic to the parental APOE Ɛ4/Ɛ4 line (UKBi011-A).

Floating-Harbor syndrome (FHS) is a rare autosomal dominant syndrome characterized by short stature with delayed bone age, retarded speech development, intellectual disability and dysmorphic facial features. Recently, dominant mutations almost exclusively clustered in the final exon of the Snf2-related CREBBP activator protein (SRCAP) gene were identified to cause FHS. Here, we report a boy with short stature, speech delay, mild intellectual disability, dysmorphic features, and with genetically confirmed FHS. To the best of our knowledge, this is the first molecularly confirmed case with this syndrome reported in Romania. An intensive program of cognitive and speech stimulation, as well as yearly neurological, psychological, ophthalmological, otorhinolaryngological, pediatric and endocrinological monitoring for our patient were designed. We propose a checklist of clinical features suggestive of FHS, based on the main clinical features, in order to facilitate the diagnosis and clinical management of this rare condition.

Floating-Harbor syndrome (FHS) is a rare autosomal dominant syndrome characterized by short stature with delayed bone age, retarded speech development, intellectual disability and dysmorphic facial features. Recently, dominant mutations almost exclusively clustered in the final exon of the Snf2-related CREBBP activator protein (SRCAP) gene were identified to cause FHS. Here, we report a boy with short stature, speech delay, mild intellectual disability, dysmorphic features, and with genetically confirmed FHS. To the best of our knowledge, this is the first molecularly confirmed case with this syndrome reported in Romania. An intensive program of cognitive and speech stimulation, as well as yearly neurological, psychological, ophthalmological, otorhinolaryngological, pediatric and endocrinological monitoring for our patient were designed. We propose a checklist of clinical features suggestive of FHS, based on the main clinical features, in order to facilitate the diagnosis and clinical management of this rare condition.

Kabuki syndrome (KS) is a rare but recognizable condition that consists of a characteristic face, short stature, various organ malformations, and a variable degree of intellectual disability. Mutations in KMT2D have been identified as the main cause for KS, whereas mutations in KDM6A are a much less frequent cause. Here, we report a mutation screening in a case series of 347 unpublished patients, in which we identified 12 novel KDM6A mutations (KS type 2) and 208 mutations in KMT2D (KS type 1), 132 of them novel. Two of the KDM6A mutations were maternally inherited and nine were shown to be de novo. We give an up-to-date overview of all published mutations for the two KS genes and point out possible mutation hot spots and strategies for molecular genetic testing. We also report the clinical details for 11 patients with KS type 2, summarize the published clinical information, specifically with a focus on the less well-defined X-linked KS type 2, and comment on phenotype–genotype correlations as well as sex-specific phenotypic differences. Finally, we also discuss a possible role of KDM6A in Kabuki-like Turner syndrome and report a mutation screening of KDM6C (UTY) in male KS patients.

Kabuki syndrome (KS) is a rare but recognizable condition that consists of a characteristic face, short stature, various organ malformations, and a variable degree of intellectual disability. Mutations in KMT2D have been identified as the main cause for KS, whereas mutations in KDM6A are a much less frequent cause. Here, we report a mutation screening in a case series of 347 unpublished patients, in which we identified 12 novel KDM6A mutations (KS type 2) and 208 mutations in KMT2D (KS type 1), 132 of them novel. Two of the KDM6A mutations were maternally inherited and nine were shown to be de novo. We give an up-to-date overview of all published mutations for the two KS genes and point out possible mutation hot spots and strategies for molecular genetic testing. We also report the clinical details for 11 patients with KS type 2, summarize the published clinical information, specifically with a focus on the less well-defined X-linked KS type 2, and comment on phenotype–genotype correlations as well as sex-specific phenotypic differences. Finally, we also discuss a possible role of KDM6A in Kabuki-like Turner syndrome and report a mutation screening of KDM6C (UTY) in male KS patients.

Efforts to identify regional-cultural differences and attempts to overcome associated potential barriers should be emphasised in any health care system when aiming for better diabetic patient care.

QUESTION UNDER STUDY: The aim of this study was to determine the prevalence of microalbuminuria (MAU) in hypertensive patients attending an office or hospital based cardiologist or internist. An additional aim was to describe associations between MAU and cardiovascular risk factors as well as to investigate the role of pharmacotherapy. METHODS: International, observational, cross-sectional study of 22282 patients with 5605 attendees in Germany and Switzerland at 444 cardiology centers. Inclusion criteria were male and female outpatients, aged > or =18 years with currently treated or newly diagnosed hypertension (> or =140/90 mm Hg at rest on the day of the study visit) and no reasons for false positive dip stick tests. The main outcome measures were the prevalence of MAU, co-morbid cardiovascular risk factors or disease and their association with the presence of MAU, and the role of pharmacotherapy in modulating prevalence of MAU. RESULTS: Prevalence of MAU in Germany and Switzerland (53.1%) was high, but lower when compared to the prevalence in "other countries" (OC, 60.2%). Routine MAU measurement was performed in 52.9% of the practices only (32.9% OC), although physicians regarded MAU to be important for risk assessment and therapeutic decisions. MAU is highly correlated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions including high waist circumference (55.1% [95%CI 56.0; 59.7]), diabetes (59.1% [56.8; 61.3]), atrial fibrillation (62.3% [57.4; 66.9]) and peripheral arterial disease (67.1% [61.6; 72.2]). Angiotensin receptor blockers (ARBs) appeared to be associated with the lowest risk of MAU (52.1%). Calcium channel blockers (CCBs) were used more frequent in patients with MAU (28.7%) than without (23.4%). CONCLUSIONS: Patients with MAU are common in clinical cardiology and its presence is associated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions. A more aggressive multi-factor