Expanding the novel MAPKAPK5-related developmental disorder's genotype-phenotype correlation: Patient report and 19 months of follow-up.

This study aimed to widen the knowledge of a recently identified, autosomal-recessive, multiple congenital anomalies syndrome to date observed in only other three children. This is the second report of biallelic mutations in MAPKAPK5 whose impairment during human development has been associated with neurological, cardiac, and facial anomalies combined with fingers and toes malformations. Through the affected patients' genetic and phenotypic features overlap, this report confirms MAPKAPK5 as causative gene and adds unique neurodevelopmental characterization. Moreover, based on the complex congenital genitourinary anomalies reported and MAPKAPK5 literature review, we also propose kidney and external genitalia involvement as a key syndromic feature whose expressivity may be more severe in males.

Exploiting in silico structural analysis to introduce emerging genotype-phenotype correlations in DHCR24-related sterol biosynthesis disorder: a case study.

Desmosterolosis is a rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, severe developmental delay, progressive epileptic encephalopathy, and elevated levels of desmosterol caused by biallelic mutations of DHCR24 encoding 3-ß-hydroxysterol Δ-24-reductase. DHCR24 is regarded as the key enzyme of cholesterol synthesis in the metabolism of brain cholesterol as it catalyzes the reduction of the Δ-24 double bond of sterol intermediates during cholesterol biosynthesis. To date, 15 DHCR24 variants, detected in 2 related and 14 unrelated patients, have been associated with the desmosterolosis disorder. Here, we describe a proband harboring the never-described DHCR24 homozygous missense variant NM_014762.4:c.506T>C, NP_055577.1:p.M169T, whose functional validation was confirmed through biochemical assay. By using molecular dynamics simulation techniques, we investigated the impact of this variant on the protein stability and interaction network with the flavin adenine dinucleotide cofactor, thereby providing a preliminary assessment of its mechanistic role in comparison to all known pathogenic variants, the wild-type protein, and a known benign DHCR24 variant. This report expands the clinical and molecular spectra of the DHCR24-related disorder, reports on a novel DHCR24 deleterious variant associated with desmosterolosis, and gives new insights into genotype-phenotype correlations.

Mobile health and implantable cardiac devices: Patients' expectations.

BACKGROUND: Mobile computing and communication technologies in health services and information (so-called mHealth) have modified the traditional approach in the follow-up of patients with implantable cardiac devices, increased patient engagement and empowerment, reduced healthcare costs and improved patients' outcome. Recent developments in mobile technology, with the introduction of smartphone-compatible devices that can measure various health parameters and transfer automatically generated data, have increased the potential application of remote monitoring and the interest towards mHealth. However, little is known about the patients' interest and expectations of this new technology. OBJECTIVE: The patients' interest in the possibility of receiving data from their implantable cardiac device, clinical and health advice via remote monitoring on their smartphones were investigated. METHODS: A questionnaire entitled 'Expectations for future possibility of self-management of device data' (Likert scale scored) was submitted to 300 consecutive implantable cardiac device outpatients. The questionnaire was focused on collecting patients' expectations in receiving direct information regarding their implantable cardiac device status (item 1, five questions), their own clinical status (item 2, seven questions) and advice on healthy lifestyle promotion (item 3, nine questions). Patient characteristics associated with greater interest towards mHealth were also investigated. RESULTS: Questionnaires were completed by 268 patients (221 men, aged 69 ± 14 years). The Cronbach test reported an alpha value of 0.98 for item 1, 0.94 for item 2 and 0.97 for item 3. Patients declared to be mainly interested in the device interventions (62%) and in severe arrhythmia occurrence (61%), followed by data on heart failure severity (54%) and their performed physical activity (48%). Patients showed very little interest in ECG tracing (37%), but the lowest interest was expressed towards healthy lifestyle promotion advice (<40%). A higher education degree and the presence of the caregiver positively affected the interest towards remote monitoring information ( P < 0.001). CONCLUSIONS: The patients' interests were mainly directed at receiving information related to technical data of the implantable cardiac device and not to the overall management of the disease, underlying the insufficient awareness of patients towards the key role of self-control health status and the promotion of a healthy lifestyle.