BACKGROUND: TBX6, a member of the T-box gene family, encodes the transcription factor box 6 that is critical for somite segmentation in vertebrates. It is known that the compound heterozygosity of disruptive variants in trans with a common hypomorphic risk haplotype (T-C-A) in the TBX6 gene contribute to 10% of congenital scoliosis (CS) cases. The deletion of chromosome 17q12 is a rare cytogenetic abnormality, which often leads to renal cysts and diabetes mellitus. However, the affected individuals often exhibit clinical heterogeneity and incomplete penetrance.
METHODS: We here present a Chinese fetus who was shown to have CS by ultrasound examination at 17 weeks of gestation. Trio whole-exome sequencing (WES) was performed to investigate the underlying genetic defects of the fetus. In vitro functional experiments, including western-blotting and luciferase transactivation assay, were performed to determine the pathogenicity of the novel variant of TBX6.
RESULTS: WES revealed the fetus harbored a compound heterozygous variant of c.338_340del (p.Ile113del) and the common hypomorphic risk haplotype of the TBX6 gene. In vitro functional study showed the p.Ile113del variant had no impact on TBX6 expression, but almost led to complete loss of its transcriptional activity. In addition, we identified a 1.85 Mb deletion on 17q12 region in the fetus and the mother. Though there is currently no clinical phenotype associated with this copy number variation in the fetus, it can explain multiple renal cysts in the pregnant woman.
CONCLUSIONS: This study is the first to report a Chinese fetus with a single amino acid deletion variant and a T-C-A haplotype of TBX6. The clinical heterogeneity of 17q12 microdeletion poses significant challenges for prenatal genetic counseling. Our results once again suggest the complexity of prenatal genetic diagnosis.

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BACKGROUND: The Koolen-de Vries syndrome (KdVS) is a relatively new rare disease caused by micro-deletion of 17q21.31 which was first reported by Koolen in 2006. Typical phenotypes for KdVS include hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Up to now, there was only one case report about anesthesia management of patient diagnosed KdVS. It was a 2-year-old girl who experienced an MRI exam under anesthesia.
METHODS: We described a 21-month-old boy who planned to undergo an orchidopexy under general anesthesia diagnosed with KdVS. He had an intellectual disability, characteristic facial dysmorphism, tracheo/laryngomalacia, patent foramen ovale, and cryptorchidism related to KdVS. Due to the complex condition especially the presence of tracheo/laryngomalacia, we took some special measures, including reducing the amount of long-acting opioid, keeping the spontaneous breath, performing a caudal block, and applying the laryngeal mask. But the laryngeal mask was changed to an endotracheal tube because it failed to provide adequate ventilation. The boy experienced mild laryngeal spasm and hypoxia after extubation, but lateral position and etomidate eased his breathing problem and re-intubation was avoided. It is indicated that anesthesia management for patients with orphan disease is a real challenge for all anesthesia providers.
CONCLUSIONS: The Koolen-de Vries syndrome is a relatively new orphan disease involving multiple systems. Keeping spontaneous breath, evaluating airway potency to anesthetics, applying endotracheal tube, and post-extubation lateral or prone position may be helpful for airway management for patient with hypotonia and tracheo/laryngomalacia. KdVS patient needs prolonged post-anesthesia monitoring and/or medication for airway complications.

IRF2BP1 breaked in the middle of exon 1 at the c.322 position and fused with RARA intron 2 which is located at 3717 bp upstream of its exon 3. The fusion produced a new intron by forming a paired splicing donor GT at 9 bp downstream of RARA breakpoint and acceptor AG at the 5\' end of RARA exon 3. The IRF2BP1::RARA fusion gene leads a fusion transcript involving IRF2BP1 exon 1 and RARA exon 3, linked by a 9-bp fragment derived from RARA intron 2. The patient with IRF2BP1::RARA has same clinical features of APL.

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OBJECTIVE: To carry out optical genome mapping (OGM) for a Chinese pedigree with a rare paracentric reverse insertion of chromosome 17.
METHODS: A high-risk pregnant woman identified at the Prenatal Diagnosis Center of Hangzhou Women\'s Hospital in October 2021 and her family members were selected as the study subjects. Chromosome G banding analysis, fluorescence in situ hybridization (FISH), single nucleotide polymorphism array (SNP array) and OGM were applied to verify the balanced structural abnormality of chromosome 17 in the pedigree.
RESULTS: Chromosomal karyotyping analysis and SNP array assay have identified a duplication of 17q23q25 in the fetus. Karyotyping analysis of the pregnant woman showed that the structure of chromosome 17 was abnormal, whilst SNP array has detected no abnormality. OGM revealed that the woman has carried a paracentric reverse insertion, which was confirmed by FISH. The karyotype of her husband was normal.
CONCLUSIONS: The duplication of 17q23q25 in the fetus has derived from a paracentric reverse insertion of chromosome 17 in its mother. OGM has the advantage for delineating balanced chromosome structural abnormalities.

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The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance. However, the genetic basis of muscle development in the Boer goat remains obscure. In this study, we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development. A total of 9 959 autosomal copy number variations (CNVs) were identified through selection signal analysis in 127 goat genomes. Specifically, we confirmed that the highest signal CNV (HSV) was a chromosomal arrangement containing an approximately 1.11 Mb (CHIR17: 60062304-61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region (CHIR17:60145940-60151302 bp) with overlapping genes (e.g., ARHGAP10, NR3C2, EDNRA, PRMT9, and TMEM184C). The homozygous duplicated HSV genotype (+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats. The expression network of three candidate genes ( ARHGAP10, NR3C2, and EDNRA) regulating dose transcription was constructed by RNA sequencing. Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells (SMSCs) and their overexpression significantly increased the expression of SAA3. The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.
作为全球畜牧业中顶级肉用经济动物品种之一，波尔山羊优异的生长性能备受各界关注。然而，至今波尔山羊优良的肌肉发育特性的遗传基础仍不清楚。该研究利用全基因组选择信号技术鉴定波尔山羊特定的结构变异并分析了其肌肉发育相关候选基因遗传基础。结果显示，在127个山羊基因组中共鉴定出9959个常染色体拷贝数变异(CNVs)。其中最高信号的CNV (HSV)是一段包含大约1.11 Mb染色体片段(CHIR17: 60062304–61171840bp)反向插入并替换一段5362bp的区域(CHIR17: 60145940–60151302bp)，并覆盖多个关键候选基因( ARHGAP10、NR3C2、EDNRA、PRMT9、TMEM184C)。基因型频率结果显示，HSV纯合变异重复基因型(+/+)在波尔山羊给群体中占96%，但在欧、亚山羊中未发现，非洲本地山羊中仅占4%的。另外，利用慢病毒转染及RNA-seq技术，构建3个主要候选基因( ARHGAP10、NR3C2和 EDNRA)的转录剂量过表达的基因调控网络，并证实这系列基因广泛参与了骨骼肌卫星细胞(SMSCs)的增殖和分化，且3个基因的过表达均显著提高了下游SAA3基因表达剂量。综上，该研究利用全基因组与细胞生物学技术手段，明晰了波尔山羊特有的结构变异HSV，并证实了其所覆盖基因可能在山羊肌肉细胞的发育具有重要作用基础，该研究将助于我们进一步理解山羊肌肉细胞的生长发育遗传机制的同时，为我国肉用山羊育种贡献了新的遗传标记。.

Male infertility is a multifactorial reproductive disorder. The effect of genetic factors on male infertility has been the focus of research. Although a variety of genetic techniques are applied to male infertility in clinical practice, karyotype analysis remains a powerful and inexpensive technology. Reciprocal chromosomal translocation (RCT) is closely related to male infertility, but the clinical phenotypes of RCT carriers are varied, and the underlying pathological mechanism is unclear. Some studies suggest that RCT breakpoints disrupt the structure and function of important genes responsible for spermatogenesis. Several breakpoints of chromosome 17 are related to important genes, which can lead to spermatogenic failure. This study aimed to identify the clinical features of 3 men with translocation karyotypes involving breakpoints on chromosome 17p13. Semen analysis and cytogenetic analysis were performed with informed consent. Gene ontology analysis was performed for 60 pathogenic genes on chromosome band 17p13. Cytogenetic analysis showed that the karyotypes were 46, XY, t(6;17) (p21;p13), 46,XY,t(10;17)(q11.2;p13), and 46, XY, t(17;20) (p13;q13), respectively. Relevant studies and genes on breakpoints on chromosome 17p13 were searched for using PubMed. Fourteen reported cases of the same karyotype were reviewed. The results suggest that although chromosome 17 is closely related to spermatogenic failure, the clinical phenotypes of RCT carriers with involvement of 17p13 breakpoints are varied. The important genes involved in the breakpoint were analyzed. The results of molecular functions suggested that these targets genes on chromosome band 17p13 were mostly involved in microfilament motor activity, ATPase activity. These results suggested that the translocation chromosome and breakpoint analysis should be considered in the clinical assessment of the patients. Physicians should be aware of these in genetic counseling. These breakpoints and the function of related genes require further study.

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