Objective:To clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes.Methods:Two patients treated at the Children′s Hospital of Henan Province respectively in June 2022 and March 2023 were selected as the study subjects. Genetic testing and diagnosis were carried out through copy number variation sequencing (CNV-seq), G-banded chromosomal karyotyping, and whole exome sequencing (WES). This study was approved by the Children′s Hospital of Henan Province (Ethics No. 2023-K-075).Results:Child 1 had mainly manifested developmental delay, white matter hypoplasia, type 1 diabetes mellitus, and micropenis. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.21q22.1)[40]/46, XY[7], and CNV-seq results showed that he has a 14.86 Mb deletion at 18p11.21p11.32 and a 14.02 Mb deletion at 18q22.1q23. Child 2 had peculiar facial features, delayed white matter myelination, developmental delay, atrial septal defect, severe sensorineural deafness, and congenital laryngeal stridor. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.2q23). CNV-seq result proved that he had a 14.86 Mb deletion at 18p11.21p11.32 and a 20.74 Mb deletion at 18q21.32q23. WES has failed to detect single nucleotide variants (SNVs) in either child, but revealed a large segmental deletion at chromosome 18 in both of them.Conclusion:Both children were diagnosed with ring chromosome 18 syndrome. The different size of the deletional fragments in the 18q region and mosaicism of ring chromosome 18 in child 1 may underlay the variation in their clinical phenotypes. The type 1 diabetes mellitus and micropenis noted in both children are novel features for ring chromosome 18 syndrome.

Objective:To investigate the clinical characteristics, genetic characteristics and diagnosis of spinocerebellar ataxia type 2 (SCA2) patients with childhood onset.Methods:The clinical data of a SCA2 pedigree who diagnosed at Neurogenetic Metabolic Disease Clinic of Children′s Hospital Affiliated to Zhengzhou University in July 2019 were collected, and the reported cases of childhood-onset SCA2 were reviewed. The CAG repeat of ATXN2 gene was detected by polymerase chain reaction, capillary gel electrophoresis and Sanger sequencing techniques.Results:A total of 9 people in 4 generations of the family were affected, showing an autosomal dominant inheritance. The proband was a 3 years and 4 months old boy, who showed abnormal symptoms at 9 months which manifested as developmental retardation. At 1 year old, he developed progressive regression which represented neither to be amused, recognize others, stand and walk alone, nor had language development. Meanwhile, he had difficulty swallowing, long-term constipation, and a history of convulsions. His sister and mother were not yet sick. His grandmother could not walk, had slurred speech accompanied by nystagmus, and magnetic resonance imaging showed cerebellar atrophy. His granduncles and grandaunts had unstable walking and dysarthria. His great-grandfather required wheelchair to walk. This pedigree showed an autosomal dominant inheritance. One of the ATXN2 gene alleles of the proband, his sister, mother and grandmother all showed abnormal amplification with 99, 55, 44, and 43 times respectively and no inserting CAA sequence. A total of 14 literatures reported 20 cases of childhood-onset SCA2 patients who were genetically diagnosed. The majorities had onset in infancy, and few can develop into school age. The main clinical manifestations were developmental delay, dystonia or insufficiency, myoclonus or infantile spasms, motor retardation, abnormal eye movement, retinitis pigmentosa and dysphagia, while the classic cerebellar syndrome was only partially present. Abnormal rhythm was found on electroencephalogram, cerebellar atrophy on magnetic resonance imaging or CT of the head.Conclusions:This case is the youngest genetically-confirmed SCA2 patient reported in China. Reported patients usually have onset in infancy with excessive repeat sequence expansion. Their clinical characteristics are different from the classic patients and could only be diagnosed by dynamic mutation detection.

Objective:To investigate the level of sleep quality among females treated firstly by IVF-ET and to find the moderate role of mindfulness in the relationship between stigma and sleep quality.Methods:From April 2018 to September 2018, we invited 380 IVF-ET females in the fertility hospital of Shandong Province to participate in the study and to finish a questionnaire survey including the Pittsburgh Sleep Quality Index(PSQI), the Mindful Attention Awareness Scale(MAAS), the simple measuring scale of stigma, and the general information questionnaire.Results:The average score of PSQI was (4.82±2.29), and the prevalence of sleep distress(PSQI>5) was 31.3%(118/380). Spearman correlation analysis showed that PSQI score was positively correlated with stigma( r=0.156, P=0.002), the infertility time( r=0.110, P=0.032), and the treatment time( r=0.142, P=0.005 ), was negatively correlated with mindfulness level( r=-0.325, P<0.001). The hierarchical regression showed that mindfulness level could moderate the correlation between stigma and sleep quality( P<0.001, Δ R2=2.8%). Furthermore, the Johnson-Neyman technique revealed that, within a specific region that was mindfulness above 72, the moderating role was significant. Conclusion:The sleep distress was common among females treated firstly by IVF-ET. Mindfulness level could moderate the correlation between stigma and sleep quality. It is suggested that the reproductive center should strengthen publicity and education to reduce the stigma level of patients, and carry out mindfulness related intervention to further improve their sleep quality.

Objective: This study aimed to investigate the present status of communication ability in reproductive nurses and explore the influencing factors, and to provide theoretical support for enhancing the infertility patients consultation satisfaction. Methods: A Convenience sample of 191 reproductive nurses were selected from Center for reproductive Medicine of Shandong University and other three general hospitals, which were assessed by questionnaires including the communication ability of nurses, the Big Five Inventory and the Jefferson Scale of Empathy. Results: The total scores of communication ability of nurses were (87.76±9.62). Communication ability was positively associated with empathy (r=0.435, P<0.01); Communication ability was negatively associated with neuroticism (r=-0.351, P<0.01) and positively associated with other dimensions of personality (r=0.196~0.433, P<0.01). Multivariate stepwise regression analysis showed that Standing in the patient′s shoes, conscientiousness and agreeableness could singnificantly predict the variance of communication ability. Conclusions The moderate communication ability were found in reproductive nurses. Standing in the patient′s shoes, conscientiousness and agreeableness were the mainly correlated factors of communication ability. The training of reproductive nurses′ empathy and personality is conducive to the improvement of communication ability.

Objective: To investigate the correlation between cord blood IgE level and allergic diseases (atopic dermatitis, food allergy, wheezing and allergic rhinitis) in 36 months old children and explore the susceptibility factors of allergy. Methods: A cohort study was designed and Cord blood was collected during delivery of 779 women with full term, and the IgE level of the sample was detected by chemiluminescence immunoassay in Department of Laboratory Medicine, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine between October 1, 2012 and May 31, 2014. 638 children were followed up at the age of 36 months. The incidence of atopic dermatitis, food allergy, wheezing and allergic rhinitis were investigated by questionnaire, and the relationship between cord blood IgE level and allergic diseases in children was analyzed by multiple logistic regression. Results: A total of 638 pregnant women and children were included in this study. The age of pregnant women was (29.7±3.3) years, and the IgE level in cord blood ranged from 0.1 to 8.43 IU/mL.In caesarean women, higher cord blood IgE was associated with increased risk of allergic dermatitis, wheezing and allergic rhinitis in children, OR=1.87, P<0.01; OR=1.86, P=0.01; OR=1.28, P=0.01; OR=1.98, P=0.01. Conclusion During cesarean section, the elevated IgE level of umbilical cord blood is correlated with the incidence of allergic diseases in children.

Objective To investigate the Fertility Quality of Life (FertiQoL) among patients with recurrent spontaneous abortion,analyze the relationships among perceived stress,psychological distress and FertiQoL,and further examine the mediating effect of psychological distress on relationships between perceived stress and FertiQoL.Methods This survey included 213 patients with recurrent spontaneous abortion from Center for Reproductive Medicine of Shandong University,which were investigated by questionnaires including FertiQoL,the Perceived Stress Scale,and the Hospital Anxiety Depression Scale.Results The total Core-FertiQoL score was (62.02 ± 14.41) points,which included four subscales as emotional,mind/body,relational and social and scored (60.01 ± 19.51),(64.28 ± 21.65),(66.57 ± 14.53),(67.57 ± 17.35) points,respectively.Perceived stress was positively associated with anxiety,depression (r =0.544,0.629,P＜0.01) and were negatively associated with FertiQoL and its four subscales (r=-0.522--0.285,P ＜0.01),and anxiety,depression was negatively associated with FertiQoL and its four subscales (r=-0.541--0.250,P＜0,01).Furthermore,Bootstrap-generated 95％CI was-0.74--0.14,P=0.003 and did not include zero,which indicated that psychological distress significantly mediated the relationship between perceived stress and FertiQoL.Conclusions Perceived stress and psychological distress could affect FertiQoL of patients with recurrent spontaneous abortion and psychological distress could mediate the relationship between perceived stress and FertiQoL.Medical staff should pay attention to not only the stress management of patients with recurrent spontaneous abortion,but also the intervention of psychological distress to improve the FertiQoL.

OBJECTIVETo carry out mutation analysis for a pedigree affected with maple syrup urine disease (MSUD).

METHODSClinical data of the proband was collected. Potential mutations of the BCKDHA and BCKDHB genes were analyzed by PCR and Sanger sequencing. Prenatal diagnosis was provided to a high-risk fetus at 12th gestational week through chorionic villus sampling.

RESULTSTwo heterozygous mutations c.284G>C (p.Gly95Ala) and c.853C>T (p.Arg285*) of the BCKDHB gene were identified in the proband, which were inherited from his mother and father, respectively. Among these, c.853C>T (p.Arg285*) was known to be pathogenic, while c.284G>C (p.Gly95Ala) was a novel mutation. Prenatal diagnosis showed that the fetus has inherited the c.284G>C (p.Gly95Ala) mutation from its mother but no mutation from its father. After birth, the infant appeared to be healthy.

CONCLUSIONThe compound heterozygous mutations c.284G>C (p.Gly95Ala) and c.853C>T (p.Arg285*) probably underlie the pathogenesis of MUSD in the proband. Mutation analysis can facilitate prenatal diagnosis and genetic counseling for the affected families.

OBJECTIVETo analyze mutations of IDUA gene in two pedigrees affected with mucopolysaccharidosis type I and provide prenatal diagnosis for them.

METHODSThe 14 exons of the IDUA gene were subjected to PCR amplification and Sanger sequencing.

RESULTSFor pedigree 1, the proband was found to harbor compound heterozygous mutations c.46-57delTCGCTCCTGGCC (p.Ser16_Ala19del) of exon 1 and c.1147delC (p.Arg383Alafs*57) of exon 8 of the IDUA gene, which were inherited from his father and mother, respectively. The latter was unreported previously. Prenatal diagnosis suggested that the fetus has carried a heterozygous c.46-57delTCGCTCCTGGCC mutation. For family 2, the proband was also found to carry compound mutations of the IDUA gene, namely c.721T to C (p.Cys241Arg) of exon 6 and c.1491delG (p.Thr497fs27) of exon 8, which were inherited from her mother and father, respectively. Neither mutation was reported previously. Prenatal diagnosis suggested that the fetus has carried a heterozygous c.721T to C mutation.

CONCLUSIONMutations of the IDUA gene probably underlie the MPS-I in both pedigrees. Above results have enriched the spectrum of IDUA gene mutations and facilitated prenatal diagnosis for both families.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; China ; DNA Mutational Analysis ; Female ; Fetal Diseases ; diagnosis ; genetics ; Heterozygote ; Humans ; Iduronidase ; genetics ; Male ; Molecular Sequence Data ; Mucopolysaccharidosis I ; diagnosis ; embryology ; genetics ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Sequence Deletion

OBJECTIVETo detect potential mutation of iduronate-2-sulfatase (IDS) gene in a family affected with mucopolysaccharidosis type Ⅱ (MPS Ⅱ).

METHODSFor the proband and his unaffected mother, the whole coding sequence of the IDS gene was analyzed with PCR and bidirectional Sanger sequencing.

RESULTSA novel splicing mutation, c.709-1G>A, was detected in the proband, for which his mother was heterozygous.

CONCLUSIONThe c.709-1G>A splicing mutation of the IDS gene is probably causative for the MSP Ⅱ in the proband. Prenatal diagnosis for the mutation may avoid birth of further child affected with this disease.

Base Sequence ; Child ; DNA Mutational Analysis ; methods ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Glycoproteins ; genetics ; metabolism ; Heterozygote ; Humans ; Iduronate Sulfatase ; genetics ; metabolism ; Male ; Mothers ; Mucopolysaccharidosis II ; diagnosis ; enzymology ; genetics ; Mutation

OBJECTIVETo analyze a patient with unexplained mental retardation by using three primer PCR (TP-PCR) and single nucleotide polymorphisms array (SNP-array), and to correlate the genotype with phenotype.

METHODSPeripheral blood sample was taken from the patient for the extraction of DNA. TP-PCR was used to determine the copy number of CGG repeats in the 5'UTR of the FMR1 gene. SNP array was used for high resolution analysis of the patient's genome.

RESULTSTP-PCR has shown no abnormal amplification of CGG in the 5'UTR of FMR1 gene. Hence, Fragile X syndrome was excluded as the cause for mental retardation. SNP array analysis has identified a 0.93 Mb duplication at 7q36.1-q36.2 and a 2.2 Mb deletion at 12p13.1-p13.2 in the patient.

CONCLUSIONThe microduplication and microdeletion discovered in the patient probably underlies the intelligence disability. The high-resolution SNP array can provide accurate information for the identification of pathogenesis, and is the preferred method for the diagnosis of unexplained mental retardation.

Child ; Cytogenetic Analysis ; Fragile X Mental Retardation Protein ; genetics ; Humans ; Intellectual Disability ; genetics ; Male ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide