Molecular characterization and evaluation of complex rearrangements in a case of ring chromosome 15

Abstract Background Ring chromosome 15 is a rare genetic entity. Only a few cases have been reported with characterization using molecular techniques. The clinical presentation is quite variable, as a result of differences in the breakpoints, haploinsufficiency of genes involved in deleted segment/s, level of mosaicism and ring instability resulting in a variability of rearrangement of genetic material. Case presentation The proband, a 2 months old boy, presented with small head size and facial dysmorphism. On examination microcephaly, triangular face, small anterior frontanelle, micrognathia, hypotonia, unilateral simian crease, hypertelorism, umbilical hernia, micropenis with mild phimosis were noted. Karyotype revealed 46,XY,r(15)(p11.2q26). Array-comparative genomic hybridization (aCGH) and targeted gene sequencing for microcephaly was carried out for genotype phenotype correlation. Array-CGH detected a 2.8 Mb terminal deletion at 15q26.3 along with a 496 kb interstitial micro-duplication, encompassing the IGF1R gene, in the affected genomic region, which was otherwise missed on conventional karyotype. Conclusion The present study highlights the importance of aCGH in not only delineating specific phenotypes through accurate genotypic correlation but also in detection and evaluation of ring chromosome with unexpected complex rearrangements

Additional file 1: of Molecular characterization and evaluation of complex rearrangements in a case of ring chromosome 15

Microcephaly panel (a total of 69 genes) was analyzed. The list of genes is mentioned. (DOCX 11 kb

Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients

Background Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge. Methods We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. Results We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function. Conclusion In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner

NEXMIF encephalopathy:an X-linked disorder with male and female phenotypic patterns

Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy

NEXMIF encephalopathy : an X-linked disorder with male and female phenotypic patterns

Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy