ABSTRACT
COL2A1 gene encodes the alpha-1 chain of type-II procollagen. Heterozygous pathogenic variants are associated with the broad clinical spectrum of genetic diseases known as type-II collagenopathies. We aimed to characterize the NM_001844.5:c.1330G>A;p.Gly444Ser variant detected in the COL2A1 gene through trio-based prenatal exome sequencing in a fetus presenting a severe skeletal phenotype at 31 Gestational Weeks and in his previously undisclosed mild-affected father. Functional studies on father's cutaneous fibroblasts, along with in silico protein modeling and in vitro chondrocytes differentiation, showed intracellular accumulation of collagen-II, its localization in external Golgi vesicles and nuclear morphological alterations. Extracellular matrix showed a disorganized fibronectin network. These results showed that p.Gly444Ser variant alters procollagen molecules processing and the assembly of mature type-II collagen fibrils, according to COL2A1-chain disorganization, displayed by protein modeling. Clinical assessment at 38 y.o., through a reverse-phenotyping approach, revealed limp gait, short and stocky appearance. X-Ray and MRI showed pelvis asymmetry with severe morpho-structural alterations of the femoral heads bilaterally, consistent with a mild form of type-II collagenopathy. This study shows how the fusion of genomics and clinical expertise can drive a diagnosis supported by cellular and bioinformatics studies to effectively establish variants pathogenicity.
ABSTRACT
Multisystemic smooth muscle dysfunction syndrome (MSMDS, OMIM # 613834) is a rare autosomal dominant condition caused by pathogenetic variants of ACTA2 gene that result in impaired muscle contraction. MSMDS is characterized by an increased susceptibility to aneurismal dilatations and dissections, patent ductus arteriosus, early onset coronary artery disease, congenital mydriasis, chronic interstitial lung disease, hypoperistalsis, hydrops of gall bladder, and hypotonic bladder. Here, we report an early diagnosis of a MSMDS related to ACTA2 p.Arg179His (R179H) mutation in a newborn and performed a review of the literature. An early diagnosis of MSMDS is extremely important, because of the severe involvement of cardiovascular system in the MSMDS. Multidisciplinary care and surveillance and timely management of symptoms are important to reduce the risk of complications.
Subject(s)
Ductus Arteriosus, Patent , Eye Diseases, Hereditary , Mydriasis , Pupil Disorders , Infant, Newborn , Humans , Ductus Arteriosus, Patent/genetics , Mydriasis/diagnosis , Mydriasis/genetics , Mutation , Eye Diseases, Hereditary/genetics , Actins/geneticsABSTRACT
Scents have the ability to affect peoples' mental states and task performance with to different extents. It has been widely demonstrated that the lemon scent, included in most all-purpose cleaners, elicits stimulation and activation, while the lavender scent elicits relaxation and sedative effects. The present study aimed at investigating and fostering a novel approach to evaluate users' experience with respect to scents' effects through the joint employment of Virtual Reality and users' neurophysiological monitoring, in particular Electroencephalography. In particular, this study, involving 42 participants, aimed to compare the effects of lemon and lavender scents on the deployment of cognitive resources during a daily life experience consisting in a train journey carried out in virtual reality. Our findings showed a significant higher request of cognitive resources during the processing of an informative message for subjects exposed to the lavender scent with respect to the lemon exposure. No differences were found between lemon and lavender conditions on the self-reported items of pleasantness and involvement; as this study demonstrated, the employment of the lavender scent preserves the quality of the customer experience to the same extent as the more widely used lemon scent.
