congenital hypothyroidism (cH) is the most common neonatal endocrine disorder with a genetic origin. The purpose of the present study was to analyze the mutation spectrum of cH patients in china. a targeted next-generation sequencing panel covering all exons of 29 cH-related causative genes was used in 43 Han chinese patients with cH [11 dysgenesis and 32 glands in situ (GiS)]. The functional impact and pathogenicity of detected variants were analyzed using a comprehensive bioinformatics approach and co-segregation studies. a total of 47 rare non-polymorphic variants in 9 target genes associated with thyroid hormone synthesis (DUOX2, DUOXA2, TPO, TG, SLC26A4 and SLC5A5), thyroid stimulating hormone resistance (TSHR) and central hypothyroidism (PROP1 and TRHR) were identified in 31 patients (31/43, 72%). of these variants, 8 were novel, including 3 in DUOX2, 2 in TPO, 3 in TSHR and 1 in SLC5A5. Variants were mostly affected by DUOX2, TG, TPO and TSHR. approximately 44% of the patients (19/43) carried DUOX2 variants. The mutation detection rates in patients with GiS were higher compared with patients with dysgenesis [25/32 (78%) vs. 6/11 (54%)]. oligogenic mutations were detected in 25.6% of the total cases and 35% of the mutated cases. Genetic basis was ascertained in 13 patients, reaching a diagnosis detection rate of 30%. in conclusion, genetic defects in dyshormonogenesis, mainly in DUOX2, were the main genetic cause of cH in the chinese population. oligogenicity is highly involved in cH pathogenesis and may thus be an important factor in common phenotypic variability observed in patients with cH.

IntroductionHigh fertility of the reproductive caste is essential for maintaining and expanding a termite colony. The most important factors for fertility of termites are thought to be the number of individuals in the reproductive caste and the copulatory selectivity of individuals in the breeding system. Life history and reproductive strategy often differ from one species to another (Lainé & Wright, 2003). The diverse and flexible breeding systems found in lower termites pre-adapt them to invade new environments or marginal habitats (Dronnet et al., 2005). Therefore, the study of the mating systems of termites has important significance to understand colony dispersal and establishment.In general, termite colonies are founded by a single primary king and a single primary queen that pair during nuptial flights, mate and subsequently produce the other colony members (Thorne et al., 1999). Since the reproductive system of termite is usually monogamous, the fecundity of the colony is AbstractReproductive systems of termite colonies may involve the number of individuals in the reproductive caste and the copulatory selectivity of reproductive individuals (i.e., polyandry or polygamy), both of them impacting directly the fertility and genetic diversity of the colony. Polygamy is widespread in the lower termites, whereas polyandry appears to be mostly absent in termites. In this paper, the differentiation of male and female neotenics was observed in orphaned experimental colonies of the subterranean termite Reticulitermes labralis. The artificial orphaned colonies began to produce neotenics only a week after colony establishing, with more neotenics appearing in the same group as time went by. Finally, each experimental group reserved multi-neotenics consisting of male and female neotenic individuals. Our results demonstrated that these neotenic individuals retained in the colony participated in reproduction. A genetic analysis at four microsatellite loci showed that in addition to the conspicuous morphologically male reproductives, there were inconspicuous males or workers that had copulated with the females in the orphaned colony. Multiple male and female reproductive individuals existed together in a single colony, and one female neotenic could mate with several male reproductives in a short time. Thus, multiple male and female reproductive systems and a polyandric mating system are present in R. labralis.

Objective Thyroid dyshormonogenesis (DH) is a genetically heterogeneous inherited disorder caused by thyroid hormone synthesis abnormalities. This study aims at comprehensively characterizing the mutation spectrum in Chinese patients with DH. Subjects and Methods We utilized next-generation sequencing to screen for mutations in seven DH-associated genes (TPO, DUOX2, TG, DUOXA2, SLC26A4, SLC5A5, and IYD) in 21 Chinese Han patients with DH from Xinjiang Province. Results Twenty-eight rare nonpolymorphic variants were found in 19 patients (90.5%), including 19, 5, 3, and 1 variants in DUOX2, TG, DUOXA2, and SLC26A4, respectively. Thirteen (62%) patients carried monogenic mutations, and six (28.5%) carried oligogenic mutations. Fifteen (71%) patients carried 2 or more DUOX2 (14) or DUOXA2 (1) variants. The genetic basis of DH in nine (43%) patients harboring biallelic or triallelic pathogenic variants was resolved. Seventeen patients (81%) carried DUOX2 mutations, most commonly p.R1110Q or p.K530X. No correlations were found between DUOX2 mutation types or numbers and clinical phenotypes. Conclusions DUOX2 mutations were the most predominant genetic alterations of DH in the study cohort. Oligogenicity may explain the genetic basis of disease in many DH patients. Functional studies and further clinical studies with larger DH patient cohorts are needed to validate the roles of the mutations identified in this study.

Epilepsy is one of the most common neurological disorders in pediatric patients with other underlying neurological defects. Identifying the underlying etiology is crucial for better management of the disorder. We performed trio-whole exome sequencing in 221 pediatric patients with epilepsy. Probands were divided into seizures with developmental delay/intellectual disability (DD/ID) and seizures without DD/ID groups. Pathogenic (P) or likely pathogenic (LP) variants were identified in 71/110 (64.5%) patients in the seizures with DD/ID group and 21/111 (18.9%) patients in the seizures without DD/ID group (P < 0.001). Eighty-seven distinct P/LP single nucleotide variants (SNVs)/insertion deletions (Indels) were detected, with 55.2% (48/87) of them being novel. All aneuploidy and P/LP copy number variants (CNVs) larger than 100 Kb were identifiable by both whole-exome sequencing and copy number variation sequencing (CNVseq) in 123 of individuals (41 pedigrees). Ten of P/LP CNVs in nine patients and one aneuploidy variant in one patient (Patient #56, #47, XXY) were identified by CNVseq. Herein, we identified seven genes (NCL, SEPHS2, PA2G4, SLC35G2, MYO1C, GPR158, and POU3F1) with de novo variants but unknown pathogenicity that were not previously associated with epilepsy. Potential effective treatment options were available for 32 patients with a P/LP variant, based on the molecular diagnosis. Genetic testing may help identify the molecular etiology of early onset epilepsy and DD/ID and further aid to choose the appropriate treatment strategy for patients.

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