Clinical, biochemical, and genetic analysis of a Chinese Han pedigree with holocarboxylase synthetase deficiency: a case report.

BACKGROUND: Holocarboxylase synthetase (HLCS) deficiency is a rare inborn disorder of biotin metabolism, which results in defects in several biotin-dependent carboxylases and presents with metabolic ketoacidosis and skin lesions. CASE PRESENTATION: In this paper, we report a Chinese Han pedigree with HLCS deficiency diagnosed by using next-generation sequencing and validated with Sanger sequencing of the HLCS and BTD genes. The Chinese proband carries the common missense mutation c.1522C > T (p.Arg508Trp) in exon 9 of the HLCS gene, which generates an increased Km value for biotin. A novel frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15) in exon 6 of the HLCS gene is predicted to be deleterious through PROVEAN and MutationTaster. A novel heterozygous mutation, c.638_642delAACAC (p.His213Profs*4), in the BTD gene is also identified. CONCLUSIONS: The Chinese proband carries the reported Arg508Trp variant, the novel 2-bp frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15), which expands the mutational spectrum of the HLCS gene, and the novel heterozygous mutation c.638_642delAACAC (p.His213Profs*4), which expands the mutational spectrum of the BTD gene. Furthermore, reversible hearing damage is rarely reported in patients with HLCS deficiency, which deserves further discussion.

[Characteristics of gene variants among patients with hyperphenylalaninemia from Quanzhou region of Fujian province].

OBJECTIVE: To explore the spectrum of genetic variants among patients with hyperphenylalaninemia (HPA) from Quanzhou area of Fujian province. METHODS: For 63 children affected with HPA, next generation sequencing was used to identify potential variants in PAH, PTS, PCBD1, QDPR, SPR and GCH1 genes. RESULTS: Fifty two variants underlying phenylalanine hydroxylase deficiency (PAHD) and 13 variants underlying 6-pyruvoyl tetrahydropterin synthase deficiency (PTPSD) were identified. Two patients carried variants of both PAH and PTS genes. The most common variants of the PAH gene were R53H (21.69%), R241C(18.07%), R243Q(12.05%) and EX6-96A to G (7.23%), which were mainly located in exons 7 (32.53%), 2 (21.69%), 6 (9.64%) and 12 (9.64%). The L227M variant of the PAH gene was unreported previously. N52S (35.00%), P87S (25.00%), IVS1-291A to G (10.00%) and T67M (10.00%) variants were the most common variants for the PTS gene and were mainly located in exons 2 (35.00%) and 5 (35.00%). CONCLUSION: The variant spectrum underlying HPA in Quanzhou area showed a geographical specificity. A novel variant of the PAH gene (L227M) has been detected.

Silk-Enabled Conformal Multifunctional Bioelectronics for Investigation of Spatiotemporal Epileptiform Activities and Multimodal Neural Encoding/Decoding.

Flexible electronics can serve as powerful tools for biomedical diagnosis and therapies of neurological disorders, particularly for application cases with brain-machine interfaces (BMIs). Existing conformal soft bioelectrodes are applicable for basic electrocorticogram (ECoG) collecting/monitoring. Nevertheless, as an emerging and promising approach, further multidisciplinary efforts are still demanded for in-depth exploitations with these conformal soft electronics toward their practical neurophysiological applications in both scientific research and real-world clinical operation. Here, clinically-friendly silk-supported/delivered soft bioelectronics are developed, and multiple functions and features valuable for customizable intracranial applications (e.g., biocompatible and spontaneously conformal coupling with cortical surface, spatiotemporal ECoG detecting/monitoring, electro-neurophysiological neural stimulating/decoding, controllable loading/delivery of therapeutic molecules, and parallel optical readouts of operating states) are integrated.

Self-Powered Multifunctional Transient Bioelectronics.

Controllable degradation and excellent biocompatibility during/after a lifetime endow emerging transient electronics with special superiority in implantable biomedical applications. Currently, most of these devices need external power sources, limiting their real-world utilizations. Optimizing existing bioresorbable electronic devices requires natural-material-based construction and, more importantly, diverse or even all-in-one multifunctionalization. Herein, silk-based implantable, biodegradable, and multifunctional systems, self-powered with transient triboelectric nanogenerators (T2 ENGs), for real-time in vivo monitoring and therapeutic treatments of epileptic seizures, are reported. These T2 ENGs are of customizable in vitro/in vivo operating life and biomechanical sensitivity via the adjustments of silk molecular size, surface structuralization, and device configuration. Functions, such as drug delivery and structural-integrity optical readout (parallel to electronic signals), are enabled for localized anti-infection and noninvasive degradation indication, respectively. A proof-of-principle wireless system is built with mobile-device readout and "smart" treatment triggered by specific symptoms (i.e., epilepsy), exhibiting the practical potential of these silk T2 ENGs as self-powered, transient, and multifunctional implantable bioelectronic platforms.

[Mutational analysis of SLC22A5 gene in eight patients with systemic primary carnitine deficiency].

OBJECTIVE: To investigate the mutations of SLC22A5 gene in patients with systemic primary carnitine deficiency (CDSP). METHODS: High liquid chromatography tandem mass spectrometry (HPLC/MS/MS) was applied to screen congenital genetic metabolic disease and eight patients with CDSP were diagnosed among 77 511 samples. The SLC22A5 gene mutation was detected using massarray technology and sanger sequencing. Using SIFT and PolyPhen-2 to predict the function of protein for novel variations. RESULTS: Total detection rate of gene mutation is 100% in the eight patients with CDSP. Seven patients had compound heterozygous mutations and one patient had homozygous mutations. Six different mutations were identified, including one nonsense mutation [c.760C>T(p.R254X)] and five missense mutations[c.51C>G(p.F17L), c.250T>A(p.Y84N), c.1195C>T(p.R399W), c.1196G>A(p.R399Q), c.1400C>G(p.S467C)]. The c.250T>A(p.Y84N) was a novel variation, the novel variation was predicted to have affected protein structure and function. The c.760C>T (p.R254X)was the most frequently seen mutation, which was followed by the c.1400C>G(p.S467C). CONCLUSION: This study confirmed the diagnosis of eight patients with CDSP on the gene level. Six mutations were found in the SLC22A5 gene, including one novel mutation which expanded the mutational spectrum of the SLC22A5 gene.