Two new cases of interstitial 7q35q36.1 deletion including CNTNAP2 and KMT2C

Abstract

Background: Terminal deletions of the long arm of chromosome 7 are well known and frequently associated with syndromic holoprosencephaly due to the involvement of the SHH (aliases HHG1, SMMCI, TPT, TPTPS, and MCOPCB5) gene region. However, interstitial deletions including CNTNAP2 (aliases Caspr2, KIAA0868, and NRXN4) and excluding the SHH region are less common. Methods: We report the clinical and molecular characterization associated with pure 7q35 and 7q35q36.1 deletion in two unrelated patients as detected by oligonucleotidebased array-CGH analysis. Results: The common clinical features were abnormal maternal serum screening during first-trimester pregnancy, low occipitofrontal circumference at birth, hypotonia, abnormal feet, developmental delay, impaired language development, generalized seizures, hyperactive behavior, friendly personality, and cranio-facial dysmorphism. Both deletions occurred de novo and sequencing of CNTNAP2, a candidate gene for epilepsy and autism showed absence of mutation on the contralateral allele. Conclusion: Combined haploinsufficiency of GALNTL5 (alias GalNAc-T5L), CUL1, SSPO (aliases SCO-spondin, KIAA0543, and FLJ36112), AOC1 (alias DAO), RHEB, and especially KMT2C (alias KIAA1506 and HALR) with monoallelic disruption of CNTNAP2 may explain neurologic abnormalities, hypotonia, and exostoses. Haploinsufficiency of PRKAG2 (aliases AAKG, AAKG2, H91620p, WPWS, and CMH6) and KCNH2 (aliases Kv11.1, HERG, and erg1) genes may be responsible of long QT syndrome observed for one patient.

Transcriptional profiling of the response to starvation and fattening reveals differential regulation of autophagy genes in mammals

“…Our data-capturing coding and non-coding transcriptomes provide a valuable resource for the identification of potential modifiers of autophagy and other important pathways affected by nutrient deprivation. This is exemplified in this study by the identification of differentially expressed lncRNAs, ATP6V0E2-AS1, RHPN1-AS1 and SLC7A11-AS1, which were recently associated with human diseases [41,54,55]. Further research will be needed to map and explore the entire spectrum of non-coding RNAs, such as circular RNAs and others, in response to fasting and fattening in mammals.…”