Pilegaardwaller3018

OBJECTIVE To explore the genetic basis for a neonate featuring global developmental delay. METHODS Clinical and laboratory tests were carried out for the patient. Peripheral venous blood samples were collected from the neonate and his parents for the extraction of DNA. Potential variant was detected by using targeted capture and next generation sequencing for a panel of genes associated with nervous system diseases. Suspected variant was validated by Sanger sequencing. RESULTS The nine-month-old boy manifested global developmental delay and was unstable to sit alone and distinguish strangers from acquaintance. Genetic testing revealed two novel variants of the SLC19A3 gene in him, namely c.448G>A and c.169C>T. The amino acids encoded by the two codons are highly conservative, and both variants were predicted to be pathogenic by bioinformatic analysis. CONCLUSION The compound heterozygous c.448G>A and c.169C>T variants probably underlay the onset of disease in the patient. Above finding also enriched the variant spectrum of SLC19A3 gene underlying Biotin-thiamine responsive basal ganglia disease.OBJECTIVE To analyze INS gene variant in a patient with maturity-onset diabetes of the young type 10. METHODS High-throughput sequencing was used to screen for the variants. Suspected variant was verified by Sanger sequencing. RESULTS Genetic testing indicated that the patient and his mother have both carried a heterozygous c.130G>A (p.Gly44Arg) variant in exon 1 of the INS gene. Prediction of protein structure suggested the variant to be pathogenic. CONCLUSION The c.130G>A (p.Gly44Arg) variant of the INS gene probably underlies the disease in this patient.OBJECTIVE To explore the genetic basis for a Chinese neonate with lipoprotein lipase deficiency. METHODS Targeted capture and next-generation sequencing (NGS) were carried out to detect variants of genes associated with inborn errors of metabolism. Suspected variants were validated by Sanger sequencing. RESULTS Genetic testing revealed novel complex heterozygous variants, namely c.347G>C (p.Arg116Pro) and c.472T>G (p.Tyr158Asp), of the LPL gene, which were respectively inherited from his father and mother. CONCLUSION Compound heterozygous variants c.347G>C and c.472T>G of the LPL gene probably underlie the lipoprotein lipase deficiency in this child.OBJECTIVE To detect variants of ARSA gene in a child featuring late infantile metachromatic leukodystrophy (MLD). METHODS PCR and Sanger sequencing was carried out for the patient and her parents. RESULTS The patient had typical features of MLD including ARSA deficiency, regression of walking ability, and demyelination. Compound heterozygous variants of the ARSA gene, namely c.960G>A and c.244C>T, were detected in the patient, for which her mother and father were respectively heterozygous carriers. ARSA c.960G>A was known to be pathogenic, while ARSA c.244C>T was a novel variant. The same variants were not detected among 50 healthy controls. CONCLUSION The compound heterozygous variants c.960G>A and c.244C>T of the ARSA gene probably underlie the MLD in this patient.OBJECTIVE To identify pathological mutation of D4Z4 in a child with facioscapulohumeral muscular dystrophy (FSHD) presented initially as mental retardation. METHODS Wechsler Intelligence Scale for Children Revised in China (WISC-IV) was used to assess the patient's IQ. Other clinical data was also collected. With genomic DNA extracted from peripheral blood samples, the child and his parents were subjected to medical exome sequencing and copy number variation analysis by next generation sequencing (NGS). The D4Z4 repeats and their origin source were determined by molecular combing. RESULTS By the WISC-IV test, the child was found to have a total IQ of 41, with a speech comprehension IQ of 45, and perceptual inference index IQ of 52. No pathological mutation was detected by NGS. By molecular combing method, the child was found to carry a D4Z4 spanning 5.2 kb with a copy number of 2. Analysis of his parents indicate that the mutation was de novo. CONCLUSION The D4Z4 copy number variation may account for the FSHD and mental retardation in the child. The molecular combing method can be used to identify the number of repeat units and facilitate the diagnosis of FSHD.OBJECTIVE To explore the genetic etiology of a girl featuring epilepsy, speech delay and mild mental retardation. METHODS Peripheral blood samples of the child and her parents were collected. Genomic DNA was extracted and subjected to next generation sequencing. Suspected variant was confirmed by Sanger sequencing. RESULTS The child was found to carry a de novo heterozygous c.3592G>A (p.V1198M) variant of the SMARCA2 gene, which was predicted to be pathogenic by bioinformatic analysis. CONCLUSION The child was diagnosed with Nicolaides-Baraitser syndrome due to heterozygous variant of the SMARCA2 gene.OBJECTIVE To explore the genetic basis for a newborn infant suspected with Donohue syndrome. METHODS Whole exome sequencing (WES) was used to screen potential variants in the child. selleck chemicals Suspected variants were validated through Sanger sequencing and real-time PCR. RESULTS The child was found to carry two heterozygous variants in the INSR gene, including c.3258+4(IVS17)A>G and deletion of exon 2, which were respectively inherited from her mother and father. CONCLUSION The compound heterozygous variants of the INSR gene probably underlie the disease in this patient.OBJECTIVE To detect potential variant in a male fetus suspected for Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate (EEC) syndrome. METHODS Peripheral blood samples of the fetus and his parents were collected for the extraction of DNA. Whole-exome sequencing was carried out to detect potential variants. Suspected variants were verified by Sanger sequencing. RESULTS The fetus was found to carry a heterozygous c.673C>T missense variant of the Tp63 gene, which was known to underlie split-hand/split-foot malformation. The same variant was not found in either parents. CONCLUSION The heterozygous c.673C>T missense variant of the Tp63 gene probably underlies the EEC syndrome in the fetus. Above finding also expanded the phenotypic spectrum for this variant.