ABSTRACT
AIM: Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated. METHODS: We studied the role(s) of cardiac Strn gene (STRN) by comparing the functional properties of CMs, generated from Strn-KO and isogenic WT mouse embryonic stem cell lines. RESULTS: The spontaneous beating rate of Strn-KO CMs was faster than WT cells, and this correlated with a larger fast INa conductance and no changes in If. Paced (2-8 Hz) Strn-KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in ICaL and IKr. Motion video tracking analysis highlighted an altered contraction in Strn-KO CMs; this was associated with a global increase in intracellular Ca2+, caused by an enhanced late Na+ current density (INaL) and a reduced Na+/Ca2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na+ channel expression and a more dynamic microtubule network in Strn-KO CMs than in WT. Indeed, incubation of Strn-KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of INa conductance toward WT levels. CONCLUSION: Loss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn-related multi-protein complexes. This leads to impaired microtubules dynamics and Na+ channels trafficking to the plasma membrane, causing a global Na+ and Ca2+ enhancement.
ABSTRACT
Syndactyly is an unusual condition in humans where two or more digits are fused together. In our report we present a case of prenatal diagnosis of simple, complete, bilateral syndactyly as the only ultrasonographic anomaly in a fetus with Down's syndrome. The mother, a 30-year-old, gravida 2, was referred to our hospital with an abnormal triple-test at 17 weeks of gestation, with a final biochemical risk for Down's syndrome more than 1:50. In this pregnancy neither the NT test nor early morphological exam showed typical findings of any chromosomal disorder. The patient underwent amniocentesis. We performed an accurate second level scan at 21 weeks while waiting for genetic results, and we suspected simple, complete, bilateral syndactyly between the third and fourth finger of the hands (rapper sign). The result of the invasive test was 47,XY,+21 and the mother opted for termination of pregnancy; the baby showed simple, complete, bilateral syndactyly of the two digits as suspected during sonography. In presenting our case report, we want to stress the importance of the accuracy of observation of fetal hand morphology, attitude, movements and reactivity. When the observation of fetal hands is not satisfactory (e.g., when the fetus does not open the fist), we recommend external stimulation of fetal reactivity through probe movements on the maternal abdomen (dynamic scan). This approach can make the identification of subtle hand anomalies easier and improve the detection rate of both structural and genetic fetal disorders.
