The impact of comorbid premenstrual syndrome or premenstrual dysphoric disorder on the clinical characteristics of bipolar disorder among Han Chinese women.

Bipolar disorder (BD) is commonly comorbid with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). However, little is known about their relationship. This study aimed to assess the impact of comorbid PMS or PMDD on the clinical characteristics of BD. A cross-sectional study was conducted on 262 women with BD. PMS and PMDD were screened with the Premenstrual Symptoms Screening Tool (PSST). Symptomatic features were assessed with Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS), and atypical features by the depressive episode section of SCID-I/P. The rates of PMS and PMDD among BD were 57.6% and 20.6% according to PSST. No significant difference in the rates of PMS and PMDD was found between BD I, BD II, and BD-NOS. Compared to BD patients without PMS or PMDD, patients with comorbid BD and PMS or PMDD were younger, more educated, had a higher risk of OCD, had an earlier age of onset, scored higher on HAMD-17 and its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and were more likely to have increased appetite and leaden paralysis. In addition, patients with comorbid BD and PMDD were less likely to experience traumatic life events, more likely to have family history of mental disorders and have inflammatory or autoimmune disease, scored higher on HMAD-17, particularly in its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and sleep disturbance. Compared with BD without PMS or PMDD, BD with PMS or PMDD might be a specific subtype of BD characterized with earlier onset age, heavier genetic load, increased symptom severity, and atypical features.

Depression and anxiety symptoms to COVID-19 outbreak among the public, medical staff and patients during the initial phase of the pandemic: an online questionnaire survey by a WeChat Mini Program.

OBJECTIVES: To survey anxiety and depression symptoms to COVID-19 outbreak in the public, medical staff and patients during the initial phase of the pandemic. DESIGN: Cross-sectional online survey administered through WeChat Mini Program using Chinese versions of Zung Self-rating Depression Scale and Zung Self-rating Anxiety Scale. SETTING: Guangzhou, China. PARTICIPANTS: 47 378 public, 1512 medical staff and 125 patients with COVID-19. RESULTS: Higher rates of depression (47.8%) and anxiety symptoms (48.7%) were shown by patients who were screened positive compared with those of the public (35.6%, 25.7%) or medical staff (15.4%, 13.3%). The professional identity of a nurse, conditions of 'with an infected family member' and 'working at the frontline' were risk factors to depression or anxiety symptoms for the medical staff. Younger age, lower educational level, female and not having adequate masks were the risk factors for the public. CONCLUSION: The COVID-19 outbreak increased people's depression or anxiety emotion responses, which varied extensively among the patients, public and medical staff.

Parallel and Scalable Heat Methods for Geodesic Distance Computation.

In this paper, we propose a parallel and scalable approach for geodesic distance computation on triangle meshes. Our key observation is that the recovery of geodesic distance with the heat method [1] can be reformulated as optimization of its gradients subject to integrability, which can be solved using an efficient first-order method that requires no linear system solving and converges quickly. Afterward, the geodesic distance is efficiently recovered by parallel integration of the optimized gradients in breadth-first order. Moreover, we employ a similar breadth-first strategy to derive a parallel Gauss-Seidel solver for the diffusion step in the heat method. To further lower the memory consumption from gradient optimization on faces, we also propose a formulation that optimizes the projected gradients on edges, which reduces the memory footprint by about 50 percent. Our approach is trivially parallelizable, with a low memory footprint that grows linearly with respect to the model size. This makes it particularly suitable for handling large models. Experimental results show that it can efficiently compute geodesic distance on meshes with more than 200 million vertices on a desktop PC with 128 GB RAM, outperforming the original heat method and other state-of-the-art geodesic distance solvers.

The Gene Polymorphism of VMAT2 Is Associated with Risk of Schizophrenia in Male Han Chinese.

OBJECTIVE: To investigate the association between gene polymorphism of vesicular monoamine transporter type 2(VMAT2) and schizophrenia in Han Chinese population. METHODS: 430 patients with schizophrenia and 470 age-sex matched controls were recruited from four mental health centers. All patients were diagnosed by two psychiatrists based on the Structured Clinical Interview for DSM Disorders (SCID). The ligase detection reactions (LDR) method was used to assess the polymorphism of the two SNPs (rs363371 and rs363324) of VMAT2. RESULTS: No associations of two SNPs with schizophrenia was found. When we stratified males and females for the analysis, we found that that in the recessive model of rs363371, there was an obvious significant association between rs363371 and schizophrenia in males (OR=0.564, 95% CI=0.357-0.892, p=0.014) but not females. For the association between rs363324 and schizophrenia, no association was found in either males or females. No association was found when stratifying early-onset schizophrenia and late-onset schizophrenia. CONCLUSION: Our findings indicate that both rs363371 and rs363324 were not associated with schizophrenia, while it seemed that the AA genotype of rs363371 plays a protective effect in male Chinese in developing schizophrenia.

Effects of Trazodone on Sleep Quality and Cognitive Function in Arteriosclerotic Cerebral Small Vessel Disease Comorbid With Chronic Insomnia.

BACKGROUND: Chronic insomnia is common in patients with arteriosclerotic cerebral small vessel disease (CSVD) and aggravates the cognitive impairment caused by CSVD. Low-dose trazodone is effective in treating insomnia, but it is unclear whether it can also improve cognitive function in CSVD patients. This study was performed to explore the effects of trazodone on sleep quality and cognitive function in CSVD comorbid with chronic insomnia. METHODS: This was a randomized, double-blind, placebo-controlled pilot study. Forty patients suffering from arteriosclerotic CSVD and insomnia were recruited from an outpatient clinic. Participants were randomized individually to receive either trazodone (study group) or a placebo (control group) for 4 weeks. The primary outcome was the cognitive score on the Montreal Cognitive Assessment scale (MoCA). Secondary outcomes included sleep parameters measured with polysomnography (PSG) and the Pittsburgh Sleep Quality Index. RESULTS: Trazodone caused significantly better improvements in concentration and recall abilities, measured with MoCA, as well as in PSG parameters such as sleep efficiency, N3 sleep ratio, and sleep continuity than the placebo, with no significant differences in the occurrence of side effects. The improvement of sleep quality was correlated with increased concentration and recall abilities. CONCLUSIONS: A low dose of trazodone seems acceptable and effective in reducing insomnia severity and improving concentration and recall abilities in this pilot study. The improvement of cognition could be achieved by alleviation of insomnia severity. Considering the high incidence of insomnia in CSVD patients, the results of this preliminary study support the use of low-dose trazodone to deal with insomnia and cognitive impairment in CSVD.

The correlation between metabolic syndrome and neurocognitive and social cognitive performance of patients with schizophrenia.

Cognitive impairment is one of the core symptoms of schizophrenia, and patients with schizophrenia are at increased risk of metabolic syndrome (MS). However, the role of MS in cognitive impairment of schizophrenia is not established. This study investigated the correlation between neurocognitive, social cognitive performance and MS with schizophrenia. One hundred and fifty eight (158) schizophrenia patients were divided into 3 groups with ① normal metabolism, ② metabolic disorder (only meeting 1 or 2 MS criteria), and ③ metabolic syndrome (meeting 3 or more MS criteria). MATRICS Consensus Cognitive Battery)MCCB(and the Brief Psychiatric Rating Scale)BPRS(were used to evaluate cognitive performance and clinical symptoms. Blood samples were obtained to detect glucose and lipid metabolic levels. Overall MCCB and subscale T scores in the normal metabolism and metabolic disorder groups were better than in the MS group. After controlling for the confounding factors including age, sex, the usage of hypolipidemic and hypoglycemic drugs, and disease duration, metabolic deficits had effects on the symbol coding and spatial span scores. The results suggest that a defective metabolic state might play a role in neurocognitive performance of schizophrenia patients.

Non breathing-related sleep fragmentation and imaging markers in patients with atherosclerotic cerebral small vessel disease (CSVD): a cross-sectional case-control study.

BACKGROUND: Sleep fragmentation was shown to be positively associated with cognitive impairment in patients with cerebral small vessel disease (CSVD); however, the underlying mechanisms are not well characterized. In this study, we sought to clarify this issue by investigating the relationship between non breathing-related sleep fragmentation and brain imaging markers in patients with CSVD. METHODS: Eighty-four CSVD patients and 24 age- and sex-matched healthy controls were prospectively recruited. All subjects underwent 3.0 T superconducting magnetic resonance imaging and overnight polysomnography. Polysomnography parameters including sleep onset latency (SOL), total sleep time (TST); sleep efficiency (SE), wake after sleep onset (WASO), percentage of each sleep stage (N1, N2, N3 and rapid eye movement [REM]), arousal index (ArI), periodic limb movement in sleep index (PLSMI), and periodic limb movement related arousal index (PLMAI) were compared between CSVD patients and healthy controls. The relationship between arousal index and CSVD markers was explored in the CSVD group. RESULTS: On polysomnography, CSVD patients showed significantly higher ArI, WASO, PLSMI, and PLMAI, and lower sleep efficiency and N- 3 ratio compared to healthy controls (p < 0.05). On ordinal logistic regression, higher ArI showed a positive association with the severity of periventricular white matter hyperintensity (odds ratio [OR] 1.121, 95% confidence interval [CI] 0.138-2.185) and perivascular space (OR 2.108, 95% CI 1.032-4.017) in CSVD patients, after adjusting for potential confounding variables. CONCLUSIONS: These preliminary results indicate that non breathing-related sleep fragmentation is common and related to the pathological markers of CSVD patients. Future prospective research is required to determine the causal relationship between sleep parameters and CSVD pathology.

Chronic Insomnia Is Associated with Higher Circulating Interleukin-8 in Patients with Atherosclerotic Cerebral Small Vessel Disease.

OBJECTIVE: Chronic inflammatory responses and leukocyte infiltration are classical pathological features of cerebral small vessel disease (CSVD). To date, limited evidence of a relationship between chronic insomnia and inflammatory responses in patients with CSVD has been uncovered. The purpose of the present study was to investigate the potential relationship between chronic insomnia and pro-inflammatory cytokine levels in patients with atherosclerotic CSVD (A-CSVD). METHODS: In total, 76 A-CSVD patients with or without chronic insomnia (CI) confirmed using magnetic resonance (MR) were prospectively recruited. Overnight polysomnography (PSG) was performed and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-17A, IL-8, and IL-12 assessed. Cytokine levels were compared between CSVD+CI (study group) and CSVD without CI (control group) patients, and the correlations between PSG parameters and cytokine levels were explored in all patients via multiple linear regression analyses. RESULTS: The serum IL-8 level of the study group (12.3±4.4 pg/mL) was significantly higher than that of the control group (7.5±2.2 pg/mL; P<0.05). PSG measurements showed that patients in the study group had significantly higher sleep onset latency (SOL), arousal index (ArI) and wake after sleep onset (WASO) as well as lower total sleep time (TST), sleep efficiency (SE) and stage 3 NREM sleep (N-3) ratio, compared with the control group (P<0.05). Multiple linear regression analyses led to the identification of ArI (ß=0.026, P<0.05) and TST (ß=-0.054, P<0.05) as significant positive and negative predictors of the IL-8 level, respectively. CONCLUSION: Chronic insomnia, in particular, sleep fragmentation and short sleep duration, may be involved in promotion of serum IL-8 expression in patients with atherosclerotic CSVD.

Zebrafish Vestigial Like Family Member 4b Is Required for Valvulogenesis Through Sequestration of Transcription Factor Myocyte Enhancer Factor 2c.

A variety of cardiac transcription factors/cofactors, signaling pathways, and downstream structural genes integrate to form the regulatory hierarchies to ensure proper cardiogenesis in vertebrate. Major interaction proteins of the transcription cofactor vestigial like family member 4 (VGLL4) include myocyte enhancer factor 2 (MEF2) and TEA domain transcription factors (TEAD), both of which play important roles in embryonic cardiac development and in adulthood. In this study, we identified that the deficiency of zebrafish vgll4b paralog, a unique family member expressed in developing heart, led to an impaired valve development. Mechanistically, in vgll4b mutant embryos the disruption of Vgll4b-Mef2c complex, rather than that of Vgll4b-Tead complex, resulted in an aberrant expression of krüppel-like factor 2a (klf2a) in endocardium. Such misexpression of klf2a eventually evoked the valvulogenesis defects. Our findings suggest that zebrafish Vgll4b plays an important role in modulating the transcription activity of Mef2c on klf2a during valve development in a blood-flow-independent manner.

The influence of non-breathing-related sleep fragmentation on cognitive function in patients with cerebral small vessel disease.

BACKGROUND: Cognitive impairment in patients with cerebral small vessel disease (CSVD) is common, but the pathogenic mechanism is not well understood. The situation of non-breathing-related sleep fragmentation in CSVD patients and its influence on cognitive impairment is not clear. The aim of this study was to investigate the influence of non-breathing-related sleep fragmentation on cognitive function in patients with CSVD. METHODS: A group of 89 CSVD patients without breathing-related sleep disorders in the Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University was enrolled. The patients underwent magnetic resonance scan, polysomnography, cognitive function evaluation using Montreal Cognitive Assessment scale (MoCA), and Mini-Mental State Examination. The patients were assigned to study group (arousal index [ArI] ≥26.8/hour) or control group (ArI <26.8/hour) based on the average level of ArI (mean =26.8, SD =7.5) at night, and the cognitive function of the patients in the two groups was analyzed. RESULTS: The total MoCA score, the subscale scores of visuospatial ability and delayed recall in the study group were significantly lower than that in the control group (P<0.05). The cognitive impairment measured by MoCA was positively related to ArI level and %N-3 sleep according to the results of logistic regression (P<0.05). CONCLUSION: Non-breathing-related sleep fragmentation is associated with cognitive impairment in CSVD patients, especially executive function and delayed recall ability.

TAMM41 is required for heart valve differentiation via regulation of PINK-PARK2 dependent mitophagy.

TAMM41, located within the congenital heart diseases (CHD) sensitive region of 3p25 deletion syndrome, is a mitochondrial membrane maintenance protein critical for yeast survival, but its function in higher vertebrates remains unknown. Via in vivo zebrafish model, we found that tamm41 is highly expressed in the developing heart and deficiency of which led to heart valve abnormalities. Molecular mechanistic studies revealed that TAMM41 interacts and modulates the PINK1-PARK2 dependent mitophagy pathway, thereby implicating TAMM41 in heart valve development during zebrafish embryonic cardiogenesis. Furthermore, through screening of the congenital heart diseases (CHD) sensitive region of 3p25 deletion syndrome among 118 sporadic atrioventricular septal defect (AVSD) patients, we identified three cases carrying heterozygous pathogenic intronic variants of TAMM41. All three cases lacked normal full-length TAMM41 transcripts, most likely due to specific expression of the mutant allele. Collectively, our studies highlight essential roles for TAMM41-dependent mitophagy in development of the heart and provide novel insights into the etiology of AVSD.

Patterns of persistence with pharmacological treatment among patients with current depressive episode and their impact on long-term outcome: a naturalistic study with 5-year follow-up.

BACKGROUND: The aim of the study was to describe and compare the patterns of medication persistence among patients with unipolar depression (UD) or bipolar depression in a 5-year follow-up, and explore their impact on long-term outcome. PATIENTS AND METHODS: A total of 333 eligible patients with current major depressive episode were observed and followed up from the first index prescription for 5 years. Lack of persistence or treatment interruption was defined as a gap of at least 2 consecutive months without taking any medication. Time to lack of persistence in the first (TLP1) and the second (TLP2) episode of treatment, number of visits before the first treatment interruption (NV) and number of treatment interruptions (NTI) were measured. RESULTS: During the 5-year follow-up, nearly 50% of patients experienced at least two times of treatment interruption. Pattern of medication persistence did not significantly differ between UD and bipolar disorder (BD) patients. TLP1 was positively associated with TLP2. Shorter TLP1 predicted a higher possibility of subsequent visits because of recurrence or relapse and more NTI meant a lower likelihood of achieving full remission in the fifth year for both UD and BD patients. For UD patients, shorter TLP1 or less NV predicted a lower chance of achieving remission, while for BD patients, shorter TLP1 meant an earlier subsequent visit and more NTI predicted a lower possibility of achieving remission. CONCLUSION: Pattern of medication persistence was similar but its impact on the long-term outcome was quite different between UD and BD.

The clinical use of chromosomal microarray analysis in detection of fetal chromosomal rearrangements: a study from China Mainland.

OBJECTIVES: This study aimed to evaluate the detection rate of chromosomal microarray analysis (CMA) in prenatal fetuses compared with conventional karyotype and to assess the additional diagnostic yields of CMA in groups of different indications. STUDY DESIGN: A total of 217 fetuses were divided into seven groups according to different indications. All cases were tested by both CMA and karyotype. The detection rates of CMA and karyotype were evaluated. The increased value of CMA in each group was also calculated. RESULTS: A total of 35 cases were detected to have a pathogenic result by CMA, indicating the overall detection rate of 16.1%. Nine more cases were detected only by CMA, indicating an incremental diagnostic yield of 4.2%. The highest incremental value was observed in fetuses with structural defects (6.6%). In 11 cases with known abnormal chromosome anomalies, CMA revealed additional information over conventional karyotyping in 4 fetuses. CONCLUSIONS: The present study convincingly demonstrated the efficiency of CMA in detecting feal chromosomal rearrangements. CMA significantly improves the detection rate in fetuses with structural defects and provides helpful information for fetuses with known abnormal chromosomes but without clear diagnosis.

Alterations of white matter fractional anisotropy in unmedicated obsessive-compulsive disorder.

BACKGROUND: Abnormalities in white matter (WM) have previously been reported in patients with obsessive-compulsive disorder (OCD). However, there was some inconsistency in the results obtained for altered regions of WM. The aim of this study was to investigate fractional anisotropy (FA) in the WM of the whole brain in patients with OCD by using diffusion tensor imaging (DTI). METHODS: In total, 28 unmedicated patients with OCD and 28 healthy volunteers underwent DTI scan. A voxel-based analysis was used to compare FA values in WM of the two groups at a voxel threshold of P<0.005 with an extent threshold of k>72 voxels (P<0.05; Alphasim correction). Subsequently, correlation analysis was conducted in order to find the correlation between the mean FA values in significantly altered brain regions and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores of the OCD patients. RESULTS: Compared with healthy volunteers, the OCD patients had lower FA value in the left lingual gyrus, right midbrain, and right precuneus. There were no regions with significantly higher FA values in OCD patients compared with healthy volunteers. The mean FA values in the above regions (left lingual, r=0.019, P=0.923; right midbrain, r=-0.208, P=0.289; and right precuneus, r=-0.273, P=0.161) had no significant correlation with the Y-BOCS scores of the OCD patients. CONCLUSION: The findings of this study suggest that alterations in WM of the left lingual gyrus, right midbrain, and right precuneus are associated with the pathophysiology mechanism of OCD, and these microstructural alterations do not correlate with symptom severity of OCD.

[Analysis of AGG interspersion of the FMR1 gene in fragile X syndrome].

OBJECTIVE: To analyze (CGG)n repeats sequence and AGG interspersion correlated with unstable expansion of FMR1 gene in a general Chinese population. METHODS: AmplideX FMR1 PCR Kit was used to amplify 380 X chromosomes from randomly selected 176 males and 102 females, 11 permutation carriers and 10 full mutation patients have served as controls. Results of capillary electrophoresis were analyzed with GeneMapper software Version 4.0. SPSS 11.0 software was used for statistical analysis. RESULTS: The ratio of heterozygous females was 64.70%. The number of alleles in general males and females was 15 and 14, the classes of AGG pattern was 26 and 27, respectively. The range of alleles was between 17 to 45 CGG repeats in males and 21 to 44 CGG repeats in females, and 1 male was identified as gray zone carrier. The most frequent allele was 29 CGG repeats, which was followed by 30 and 36 repeats, while 28 CGG repeats were absent. The most common AGG pattern was 9A9A9, 99.21% of the population was detected with different forms and numbers of AGG interruption, and 6A interruption pattern was found in 10.02% samples especially in individuals with more CGG repeats. However, 57.58% of control samples had no AGG interruption, and none of the controls had 6A interruption pattern. No significant difference was observed in allele frequent distribution of (CGG)n repeats and AGG interspersion patterns between the males and females (P > 0.05), and AGGs was significantly different between general population and controls (P < 0.05). CONCLUSION: AGGs and AGG pattern may have important roles in maintaining (CGG)n stability in general population of China, 9A9A6A9 may be a special pattern for preventing (CGG)n unstable expansion in Asian populations.

[The resting-state functional connectivity of the hypothalamus and its relationships with gonadal steroid hormones and depression symptoms in perimenopausal women].

OBJECTIVE: This study aimed to investigate the resting-state functional connectivity of the hypothalamus and its relationships with gonadal steroid hormones and depression symptoms in perimenopausal women. METHODS: Total 66 perimenopausal women voluntarily participated in this study from October 2012 to June 2013. Zung Self-rating Depression Scale (ZSDS) was used to assess depression symptoms. Plasma gonadal steroid hormones including estradiol, testosterone, and progesterone were determined by the chemiluminescence immunoassay. A 3.0 Tesla magnetic resonance imaging (MRI) scanner was utilized to acquire resting-state functional MRI data. The z-value functional connectivity map of each participant was calculated voxel-wisely based on the seed region of the hypothalamus. One sample t test of Statistical Parametric Mapping (SPM) were used to determine the brain areas with statistically significant functional connectivity to the hypothalamus, then multiple regression of SPM was used to calculate the correlated areas with 3 gonadal steroid hormones, respectively. Finally, Pearson correlation was performed to analyze bivariate correlations between mean z-values and ZSDS scores. RESULTS: Significant functional connectivity to the hypothalamus were found in brain areas as follows:the lateral inferior frontal gyrus, medial prefrontal cortex, dorsal lateral prefrontal cortex, orbitofrontal cortex, subgenual cortex, anterior cingulate cortex, posterior cingulate cortex, cuneus and precuneus, hippocampus and parahippocampal gyrus, and angular gyrus (False Discovery Rate q<0.05). Among these areas, the plasma testosterone level was positively related to the functional connectivity strength of the right angular gyrus, and negatively related to the strengths of the right subgenual cortex and bilateral medial superior frontal gyrus to the hypothalamus (PAlphaSim<0.05). Especially, mean z-value in the subgenual cortex was positively related to the ZSDS index score (r=0.279, P=0.023), and factor scores of the core depression symptoms (r=0.278, P=0.024) and somatic symptoms (r=0.357, P=0.003). CONCLUSION: In perimenopausal women, the hypothalamus has resting-state functional connectivity with widespread areas involved in the brain depression-related network and default mode network, and the plasma androgen level may modulate the functional connectivity strengths of the hypothalamus and decrease the susceptibility of perimenopausal women to depression.

Alterations in white matter fractional anisotropy in subsyndromal perimenopausal depression.

BACKGROUND: Subsyndromal depression (SSD) is considered as a predictor for future depressive disorders, however whether white matter abnormalities are involved in the high-susceptibility of women to depressive disorders during perimenopause is unknown. The purpose of this study was to investigate fractional anisotropy (FA) in the white matter of the whole brain in perimenopausal women with SSD using diffusion tensor imaging (DTI). METHODS: In a cross-sectional study, 24 perimenopausal women with SSD and 24 other age-, education-, and body mass index-matched healthy women underwent DTI. A voxel-based analysis was used to elucidate regional FA changes at a voxel threshold of p < 0.001 with an extent threshold of k > 127 voxels (p < 0.05, AlphaSim correction). Subsequently, correlation analyses were performed between mean FA values in significant brain regions and plasma estradiol level. RESULTS: Compared to healthy controls, women with SSD exhibited significantly lower FA values in the left insula, while higher FA values were observed in the left ventral lateral thalamus and left and right brainstem in the midbrain. In subjects with SSD, the mean FA value in the left insula was positively correlated to plasma estradiol levels (r = 0.453, p = 0.026) (uncorrected). CONCLUSIONS: Our findings indicate altered microstructures in white matter of the insula and subcortical regions may be associated with the high susceptibility of perimenopausal women to depressive disorders. Estrogen may modulate the white matter microstructure of the insula.

A novel mutation in MID1 in a patient with X-linked Opitz G/BBB syndrome.

Opitz G/BBB syndrome (OS) is a genetically heterogeneous disease. We report on an OS patient with a novel inherited mutation in MID1. Metaphase analysis showed a normal male karyotype. Array CGH revealed a maternally inherited duplication at Xp22.31 (6,467,203-7,992,261, hg18), the size was estimated to 1.5Mb. Sequence analysis of the MID1 coding region revealed a novel missense mutation in exon 8 (c.1561C>T/p. R521C) which resulted in an ammonia acid substitution (R521C) in the PRX domain of the MID1 protein. The mutation was inherited from unaffected grandmother and mildly affected mother. Prenatal diagnosis was performed for the third pregnancy after identification of the causative mutation in the family. The third fetus was found to be a female carrier. Postnatal follow-up at 2-month-old showed normal phenotype. In conclusion, we reported a familial OS patient with a novel mutation in exon 8 which provided another evidence for that mutation clustered in C-terminal domain of MID1. The newly identified mutation in our patient expands mutation spectrum in MID1 gene.

[Unbalanced subtelomic rearrangement involving 9q and 22q in a child with mental retardation and multiple congenital anomalies].

OBJECTIVE: To determine genetic cause for a patient with development delay and multiple congenital anomalies. METHODS: Routine karyotype analysis was performed for the patient and his parents. Array comparative genomic hybridization (array CGH) was performed for the patient to detect cryptic chromosome aberration. RESULTS: Karyotype analysis revealed no obvious anomaly for the patient and his parents. Array CGH has detected a 2.8 Mb heterozygous deletion at 9q34.3 and an 8.1 Mb heterozygous duplication at 22q. Fluorescence in situ hybridization analysis of the patient revealed an unbalanced subtelomeric translocation 46, XY, der(9) t(9; 22) (q34.3; q13.2q13.33) mat, which has resulted in partial trisomy 22q and partial monosomy 9q. Clinical features of the patient included developmental delay, facial dysmorphism and multiple congenital anomalies. Upon subsequent pregnancy, FISH analysis revealed that the fetus has inherited the normal chromosomes 9 and 22 from his mother. Postnatal follow-up confirmed normal development milestone and physiques in the child. CONCLUSION: An unbalanced translocation involving 9q and 22q has been found in a child featuring multiple congenital anomalies, which is due to a balanced translocation 9; 22 in his mother. Array CGH and FISH have also helped with discovery of subtelomeric rearrangement. Prenatal diagnosis of this aberration in subsequent pregnancies with FISH can prevent the recurrence of this disease.