Genetic testing for ventricular septal defect

Abstract Ventricular septal defects (VSDs) are the commonest heart malformations and may affect the membranous or the muscular septum. Clinical presentation depends on the amount of interventricular flow, which is determined by the size of the defect and the relative resistances of the pulmonary and systemic vascular beds. The prevalence of VSD is estimated at about 5% among infants. Many small malformations present at birth may later undergo spontaneous closure. VSD may have autosomal dominant or autosomal recessive inheritance and may exist as isolated forms or as part of a syndrome. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Genetic testing for atrioventricular septal defect

Abstract Atrioventricular septal defect (AVSD) is a congenital heart defect characterized by a shared atrioventricular junction coexisting with deficient atrioventricular septation. The main morphological characteristic of AVSD is a common atrioventricular canal. The prevalence of AVSD is estimated at 0.31/1000 live births and is higher among subjects with PTPN11 mutations. ASD may have autosomal dominant or autosomal recessive inheritance. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Genetic testing for vascular anomalies

Abstract Vascular anomalies (VAs) have phenotypic variability within the same entity, overlapping clinical features between different conditions, allelic and locus heterogeneity and the same disorder can be inherited in different ways. Most VAs are sporadic (paradominant inheritance or de novo somatic or germline mutations), but hereditary forms (autosomal dominant or recessive) have been described. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Liquid levothyroxine formulations in patients taking drugs interfering with L-T4 absorption

PurposeTo describe the current knowledge on thyroid hormonal profile in patients on liquid L-T4 therapy and drugs known to interfere with L-T4 absorption. MethodsA PubMed/MEDLINE, Web of Science, and Scopus research was performed. Case reports, case series, original studies and reviews written in English and published online up to 31 August 2022 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review. ResultsThe available data showed that novel levothyroxine formulations circumvent gastric pH impairment due to multiple interfering drugs such as proton pump inhibitors, calcium or iron supplements, sevelamer, aluminum/magnesium hydroxide and sodium alginate. ConclusionNew formulations can be taken simultaneously with drugs interfering with L-T4 absorption, in particular liquid formulations. Softgel capsules need more studies to support these data

Novel loss-of-function variants in filaggrin exon 3 in patients with severe atopic dermatitis

The strongest genetic risk for atopic dermatitis (AD) is variants in the filaggrin gene (FLG). FLG encodes a large protein called profilaggrin, i.e. the precursor of filaggrin which plays a multifaceted role in maintaining skin barrier function by contributing to hydration via natural moistur- izing factor formation, corneocyte structural integrity, pH regulation, antimicrobial defence, and lipid barrier forma- tion [1]. FLG consists of 2 introns and 3 exons. The third exon is the largest and the chief coding element. The iden- tification of causative variants is challenging, due to high sequence homology within the 10 to 12 tandem repeats [2]. The primary objective of this study is to assess the variant frequency of FLG in patients with severe AD vs. healthy individuals

Neuropsychological Alterations in Children Affected by Obstructive Sleep Apnea Syndrome

Sleep-related breathing disorders are a group of clinical conditions ranging from habitual snoring to obstructive sleep apnea syndrome (OSAS) during the lifespan. In children, other risk factors are represented by adenotonsillar hypertrophy, rhinitis, nasal structure alteration, cleft palate, velopharyngeal flap surgery, pharyngeal masses, craniofacial malformations, genetic syndrome (i.e. Down syndrome, Crouzon syndrome, and Apert syndrome), genetic hypoplasia mandibular (i.e. Pierre Robin syndrome, Treacher Collins syndrome, Shy-Drager syndrome, and Cornelia De Lange syndrome), craniofacial traumas, chronic or seasonal rhinitis, asthma, neuromuscular syndromes, brainstem pathologies (i.e. Arnold-Chiari malformation and Joubert syndrome), achondroplasia, and mucopolysaccharidosis. OSAS may affect the executive functioning such as motivational ability, planning, behavior modulation, ability to complete an action program, identification of functional strategies to achieve the goal, problem solving, flexibility, monitoring and self-assessment of behavior in relation to results, change of task, or behavior in the light of emerging information, which may be all impaired by nocturnal intermittent hypoxia also during the developmental age. The clinical presentation of OSAS can mimic other neurobehavioral symptoms, such as ADHD syndrome, learning problems, or can exacerbate the Fragile X syndrome, and generalized non-convulsive epilepsy symptoms

Validation of an intra-oral scan method versus cone beam computed tomography superimposition to assess the accuracy between planned and achieved dental implants: a randomized in vitro study

Computer aided implantology is the safest way to perform dental implants. The research of high accuracy represents a daily effort. The validated method to assess the accuracy of placed dental implants is the superimposition of a pre-operative and a post-operative cone beam computed tomography (CBCT) with planned and placed implants. This procedure is accountable for a biologic cost for the patient. To investigate alternative procedure for accuracy assessment, fifteen resin casts were printed. For each model, six implants were digitally planned and then placed following three different approaches: (a) template guided free hand, (b) static computer aided implantology (SCAI), and (c) dynamic computer aided implantology (DCAI). The placement accuracy of each implant was performed via two methods: the CBCT comparison described above and a matching between implant positions recovered from the original surgical plan with those obtained with a post-operative intraoral scan (IOS). Statistically significant mean differences between guided groups (SCAI and DCAI) and the free hand group were found at all considered deviations, while no differences resulted between the SCAI and DCAI approaches. Moreover, no mean statistically significant differences were found between CBCT and IOS assessment, confirming the validity of this new method

Neuropsychological Alterations in Children Affected by Obstructive Sleep Apnea Syndrome

Sleep-related breathing disorders are a group of clinical conditions ranging from habitual snoring to obstructive sleep apnea syndrome (OSAS) during the lifespan. In children, other risk factors are represented by adenotonsillar hypertrophy, rhinitis, nasal structure alteration, cleft palate, velopharyngeal flap surgery, pharyngeal masses, craniofacial malformations, genetic syndrome (i.e. Down syndrome, Crouzon syndrome, and Apert syndrome), genetic hypoplasia mandibular (i.e. Pierre Robin syndrome, Treacher Collins syndrome, Shy-Drager syndrome, and Cornelia De Lange syndrome), craniofacial traumas, chronic or seasonal rhinitis, asthma, neuromuscular syndromes, brainstem pathologies (i.e. Arnold-Chiari malformation and Joubert syndrome), achondroplasia, and mucopolysaccharidosis. OSAS may affect the executive functioning such as motivational ability, planning, behavior modulation, ability to complete an action program, identification of functional strategies to achieve the goal, problem solving, flexibility, monitoring and self-assessment of behavior in relation to results, change of task, or behavior in the light of emerging information, which may be all impaired by nocturnal intermittent hypoxia also during the developmental age. The clinical presentation of OSAS can mimic other neurobehavioral symptoms, such as ADHD syndrome, learning problems, or can exacerbate the Fragile X syndrome, and generalized nonconvulsive epilepsy symptoms

RP1 Dominant p.Ser740* Pathogenic Variant in 20 Knowingly Unrelated Families Affected by Rod–Cone Dystrophy: Potential Founder Effect in Western Sicily

BACKGROUND AND OBJECTIVES: Retinitis pigmentosa (RP) is the most common inherited rod–cone dystrophy (RCD), resulting in nyctalopia, progressive visual field, and visual acuity decay in the late stages. The autosomal dominant form (ADRP) accounts for about 20% of RPs. Among the over 30 genes found to date related to ADRP, RP1 pathogenic variants have been identified in 5–10% of cases. In a cohort of RCD patients from the Palermo province on the island of Sicily, we identified a prevalent nonsense variant in RP1, which was associated with ADRP. The objective of our study was to analyse the clinical and molecular data of this patient cohort and to evaluate the potential presence of a founder effect. MATERIALS AND METHODS: From 2005 to January 2023, 84 probands originating from Western Sicily (Italy) with a diagnosis of RCD or RP and their relatives underwent deep phenotyping, which was performed in various Italian clinical institutions. Molecular characterisation of patients and familial segregation of pathogenic variants were carried out in different laboratories using Sanger and/or next-generation sequencing (NGS). RESULTS: Among 84 probands with RCD/RP, we found 28 heterozygotes for the RP1 variant c.2219C>G, p.Ser740* ((NM_006269.2)*, which was therefore significantly prevalent in this patient cohort. After a careful interview process, we ascertained that some of these patients shared the same pedigree. Therefore, we were ultimately able to define 20 independent family groups with no traceable consanguinity. Lastly, analysis of clinical data showed, in our patients, that the p.Ser740* nonsense variant was often associated with a late-onset and relatively mild phenotype. CONCLUSIONS: The high prevalence of the p.Ser740* variant in ADRP patients from Western Sicily suggests the presence of a founder effect, which has useful implications for the molecular diagnosis of RCD in patients coming from this Italian region. This variant can be primarily searched for in RP-affected subjects displaying compatible modes of transmission and phenotypes, with an advantage in terms of the required costs and time for analysis. Moreover, given its high prevalence, the RP1 p.Ser740* variant could represent a potential candidate for the development of therapeutic strategies based on gene editing or translational read-through therapy for suppression of nonsense variants