Identification of LINS1 gene variant in a patient with severe mental retardation / 中华医学遗传学杂志

Objective@#To explore the genetic basis of a child with idiopathic mental retardation.@*Methods@#Clinical data and peripheral blood sample of the child were collected. Genomic DNA was extracted and subjected to copy number analysis using single nucleotide polymrophism array comparative genome hybridization (SNP-aCGH) and targeted capture and next generation sequencing (NGS).@*Results@#No microdeletion/microduplication were detected by SNP-aCGH. NGS has detected homozygous c. 722delA(p.Asp241fs) variant of the LISN1 gene, which is known to underlie autosomal recessive mental retardation - 27 (MRT 27). Both parents are carriers of the variant, conforming to the autosomal recessive inheritance.@*Conclusion@#A novel pathogenic variant of the LINS1 gene has been identified, which probably underlies the MRT 27 in the patient.

Rapid identification of pathogenic mutations in sporadic hereditary retinal dystrophies using targeted next-generation sequencing / 中华实验眼科杂志

Background Hereditary retinal diseases (HRDs) are a group of retinal degenerative diseases with significant genetic and clinical heterogeneities.Traditional techniques are challenging for detection of pathogenic mutations.Objective This study was to identify the diseasing-causal genes in 20 Chinese families with a variety of HRDs.Methods Family histories and ophthalmic examinations were obtained from all participants in 20 sporadic families.Targeted sequence capture array technique with next-generation sequencing (NGS) was performed to detect pathogenic mutations in 232 identified genes associated with HRDs.Variants detected by NGS were filtered by bioinformatic analysis HRDs.Genotype-phenotype correlation was also assessed.Results We identified 11 patients with pathogenic mutations,including 8 compound heterozygous mutations and 3 homozygous mutations,which were not yet reported.These findings showed genetic diagnoses in 11 of 20 patients,with the positive rate of 55％.Among them,6 patients were autosomal recessive inheritance and 5 were unspecific.Identification of different mutations and divergent phenotypes revealed 5 patients were affected with cone-rod dystrophy,3 patients with Leber congenital amaurosis,1 patient with congenital stationary night blindness,1 patient with Best vitelliform macular dystrophy and 1 patient with Stargardt disease.Conclusions Targeted NGS is an effective approach for the genetic diagnoses of HRDs.These findings provide insights into understanding the genotype-phenotype correlations in HRDs.