[Clinical phenotypic and genotypic analysis of 5 pediatric patients with ß-ketothiolase deficiency].

Objective: To summarize the clinical and genetic characteristics of children with ß-ketothiolase deficiency (BKTD). Methods: The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children's Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed. Results: The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 µmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant. Conclusions: ß-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of ß-ketothiolase deficiency.

The relationship between the levels and function of endothelial progenitor cells and factor V Leiden and protein C deficiency in patients with primary Budd-Chiari syndrome.

OBJECTIVE: Budd-Chiari syndrome (BCS) is a life-threatening hepatic disease characterized by hepatic venous obstruction at the level of hepatic vein, hepatic venules, or inferior vena cava. No evidence reported the relationship between the endothelial progenitor cells and the deficiency of factor V Leiden and protein C in patients with primary Budd-Chiari syndrome. PATIENTS AND METHODS: We recruited participants between June 2014 and July 2015. For primary BCS group, 28 patients were collected. 20 patients were included in the NAFLD group. Another 73 healthy participants were recruited into the control group. None of the patients and participants had received interventional therapy or had undergone surgery prior to being recruited. Levels and functions of endothelial progenitor cells (EPCs) were examined. The factor V Leiden mutation, protein C deficiency and protein S deficiency were evaluated. Finally, the relationship between the levels and function of endothelial progenitor cells and factor V Leiden and protein C deficiency in patients with primary Budd-Chiari syndrome was analyzed. RESULTS: The results showed that no significant differences were found between the BCS (and NAFLD) and control group considering age, sex, BMI, smoking (p>0.05 for variables). However, significant differences were observed in TG, TC, HDL-C, white blood cells, hemoglobin, ALT, AST, ALP, γ-GT, total bilirubin, and albumin (p<0.05 for variables). Compared with the healthy participants, significant downregulation was found in BCS and NAFLD patients regarding CD34+/CD45-, late outgrowth endothelial cells (OECs) colonies, OECs proliferation, and OECs tubulogenesis (p<0.001 for variables). Among the 28 BCS patients, factor V Leiden mutation (n=10, 35.71%, OR 12.67, 95% CI 5.24-27.93) and hereditary protein C deficiency (n=4, 14.29%, OR 7.48, 95% CI 2.02-21.43) were more prevalent than those in the control group. These results suggested that factor V Leiden mutation and protein C deficiency were major risk factors for BCS. Finally, we demonstrated that factor V Leiden and protein C deficiency may negatively regulate the OECs levels and functions in BCS patients. CONCLUSIONS: It's important to improve the OECs levels and functions, and to prevent the deficiency of factor V Leiden and protein C in the treatment of BCS.

Chain of rings: a radiographic sign of papillary thyroid cancer.

Papillary thyroid cancer is the most common form of thyroid malignancy in children and adult with frequent metastases to the cervical lymph nodes. We present a case of metastatic papillary thyroid cancer with remarkable imaging findings of consecutive metastatic calcified lymph nodes resembling a chain of rings. While accompanying by a coarsely calcified thyroid mass, possible thyroid cancer should be considered and serve as a guide to warrant further thyroid cancer evaluation.

Curcumin-mediated oxidative stress resistance in Caenorhabditis elegans is modulated by age-1, akt-1, pdk-1, osr-1, unc-43, sek-1, skn-1, sir-2.1, and mev-1.

Abstract Curcumin (diferuloylmethane), a pharmacologically active substance derived from turmeric, exhibits anti-inflammatory, anticarcinogenic, and antioxidant properties. We examined the modulation of oxidative-stress resistance and associated regulatory mechanisms by curcumin in a Caenorhabditis elegans model. Our results showed that curcumin-treated wild-type C. elegans exhibited increased survival during juglone-induced oxidative stress compared with the control treatment. In addition, curcumin reduced the levels of intracellular reactive oxygen species in C. elegans. Moreover, curcumin induced the expression of the gst-4 and hsp-16.2 stress response genes. Lastly, our findings from the mechanistic study in this investigation suggest that the antioxidative effect of curcumin is mediated via regulation of age-1, akt-1, pdk-1, osr-1, unc-43, sek-1, skn-1, sir-2.1, and mev-1. Our study elucidates the diverse modes of action and signaling pathways that underlie the antioxidant activity exhibited by curcumin in vivo.

Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis.

BACKGROUND: The aim was to evaluate the diagnostic value of procalcitonin, C-reactive protein (CRP) and white blood cell count (WBC) in uncomplicated or complicated appendicitis by means of a systematic review and meta-analysis. METHODS: The Embase, MEDLINE and Cochrane databases were searched, along with reference lists of relevant articles, without language restriction, to September 2012. Original studies were selected that reported the performance of procalcitonin alone or in combination with CRP or WBC in diagnosing appendicitis. Test performance characteristics were summarized using hierarchical summary receiver operating characteristic (ROC) curves and bivariable random-effects models. RESULTS: Seven qualifying studies (1011 suspected cases, 636 confirmed) from seven countries were identified. Bivariable pooled sensitivity and specificity were 33 (95 per cent confidence interval (c.i.) 21 to 47) and 89 (78 to 95) per cent respectively for procalcitonin, 57 (39 to 73) and 87 (58 to 97) per cent for CRP, and 62 (47 to 74) and 75 (55 to 89) per cent for WBC. ROC curve analysis showed that CRP had the highest accuracy (area under ROC curve 0·75, 95 per cent c.i. 0·71 to 0·78), followed by WBC (0·72, 0·68 to 0·76) and procalcitonin (0·65, 0·61 to 0·69). Procalcitonin was found to be more accurate in diagnosing complicated appendicitis, with a pooled sensitivity of 62 (33 to 84) per cent and specificity of 94 (90 to 96) per cent. CONCLUSION: Procalcitonin has little value in diagnosing acute appendicitis, with lower diagnostic accuracy than CRP and WBC. However, procalcitonin has greater diagnostic value in identifying complicated appendicitis. Given the imperfect accuracy of these three variables, new markers for improving medical decision-making in patients with suspected appendicitis are highly desirable.

Unusual manifestations of vertebral osteomyelitis: intraosseous lesions mimicking metastases.

BACKGROUND AND PURPOSE: Vertebral osteomyelitis can have different imaging manifestations. The purpose of this study was to demonstrate the unusual MR imaging patterns of vertebral osteomyelitis with intraosseous lesions mimicking metastases. MATERIALS AND METHODS: From September 2000 to August 2007, 7 patients were selected from our data base of 214 patients with confirmed vertebral osteomyelitis and MR images. All of those having misinterpreted MR imaging reports and unusual imaging patterns were analyzed. The presence of a peripheral curvilinear area of low signal intensity in an osseous lesion (the rim sign) and a peripheral rim of high signal intensity on T2-weighted images around an osseous lesion (the halo sign) was evaluated. Follow-up MR imaging studies were performed in all patients. RESULTS: The patients were 5 men and 2 women, with an age range of 42-80 years. MR imaging findings of those with vertebral osteomyelitis showed a solitary lesion in 2 and multiple lesions in 5 patients. The intraosseous lesions revealed low signal intensity on T1-weighted images, mixed or high signal intensity on T2-weighted images, high signal intensity on short tau inversion recovery images, and global or marginal enhancement. The rim sign was found in 6 (86%) patients; halo sign, in 7 (100%); preserved intervertebral disks, in 7 (100%); and limited paraspinal or epidural inflammation, in 6 (86%). Images of all patients demonstrated healing or almost healed changes on the follow-up MR imaging studies. CONCLUSION: Vertebral osteomyelitis can have MR imaging patterns mimicking osseous metastases. Recognition of these unusual imaging manifestations, together with clinical and histopathologic analysis, may aid in reaching the correct diagnosis.

Cytokine gene polymorphisms in Chinese patients with psoriasis.

BACKGROUND: Previous studies have shown that cytokine gene polymorphisms may confer susceptibility to psoriasis. OBJECTIVES: To determine whether genetic polymorphisms of the cytokine genes might influence the development of psoriasis in Chinese patients in Taiwan. METHODS: DNA samples were obtained from 170 patients with psoriasis vulgaris (PV), 102 patients with psoriatic arthritis (PsA) and 210 control subjects. Using direct sequencing and microsatellite genotyping, we examined 28 polymorphisms in 11 cytokine genes including the interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-8, IL-10, IL-12B, IL-13, tumour necrosis factor (TNF)-alpha, TNF-beta and interferon-gamma genes. Genotypes of HLA-Cw*0602, killer cell immunoglobulin-like receptor (KIR) genes and major histocompatibility complex class I chain-related gene A (MICA) were also determined in patients with PsA. RESULTS: The patients with PV were more likely to carry the +4496G allele of the IL-12B gene (59.4% vs. 49.3%, P = 0.0067, P(c) = 0.033). However, no significantly different allelic and genotypic distributions of the other analysed genes including IL-1beta, TNF-alpha, TNF-beta, KIR genes and MICA were found between the PV/PsA patients and controls. Moreover, no association was observed with disease onset, gender, peripheral arthritis or joint erosion. With regards to HLA-Cw*0602, its allele frequency was significantly increased in patients with early-onset PV (25.3% vs. 4.8%, P < 10(-7)), but not in patients with PsA. CONCLUSIONS: The IL-12B gene polymorphism conferred a risk for PV in our Chinese population, although the effect was more minor than that of HLA-Cw*0602. Cw*0602, KIR2DS1/S2 and MICA-A9 were unlikely to be risk alleles in our patients with PsA. The other analysed genetic polymorphisms of cytokine genes do not appear to be associated with susceptibility to PV and PsA in Chinese patients in Taiwan.

No association of cytokine gene polymorphisms in Chinese patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronically relapsing skin disease associated with the activation of T-helper 2 cells. Recent studies have shown that polymorphisms in the genes for interleukin (IL)-4, the IL-4 receptor, IL-13, and signal transducer and activator 6 (STAT6) may contribute to susceptibility of AD. To date, no cytokine gene polymorphism study has been conducted on Chinese patients with AD. AIMS: To determine whether genetic polymorphisms of the cytokine genes might influence the development of AD. METHODS: DNA samples were obtained from 94 patients and 186 control subjects. Using direct sequencing and microsatellite genotyping, we examined 22 polymorphisms in eight cytokine genes including the genes for IL-4, -10, -12B and -13, the IL-4 receptor, tumour necrosis factor (TNF)-alpha, STAT6, and interferon (IFN)-gamma. RESULTS: No significantly different allelic and genotypic distributions of the cytokine gene polymorphisms could be found between patients and controls. Moreover, no association was observed with disease onset, gender, the presence of elevated serum total IgE level or blood eosinophilia. CONCLUSION: Our study suggests that the analysed genetic polymorphisms of cytokine genes do not appear to be associated with AD susceptibility in our Chinese population.

Cytokine gene polymorphisms in bullous pemphigoid in a Chinese population.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune bullous disease mostly associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and BP230. High levels of interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms may affect cytokine production and contribute to susceptibility to autoimmune diseases. Until now, no cytokine gene polymorphism study has been conducted on patients with BP. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the cytokine genes might influence the development of BP. METHODS: DNA samples were obtained from 96 BP patients and 174 control subjects. Using direct sequencing and microsatellite genotyping, we examined 23 polymorphisms in 11 cytokine genes including the IL-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-alpha and IFN-gamma genes. RESULTS: Although the BP patients were more likely to carry the -511T and -31C alleles of the IL-1beta gene (P = 0.04), the significance disappeared after correction for multiple testing (Pc). There was complete linkage disequilibrium between the -511T and -31C alleles of the IL-1beta gene. In female patients with BP, the associations with IL-1beta (-511T) and (-31C) alleles were much stronger (68% vs. 40.6%, odds ratio = 3.11, Pc = 0.006). No significantly different allelic and genotypic distributions of other cytokine gene polymorphisms could be found between the patients with BP and controls. Moreover, no association with the extent of disease involvement (localized or generalized) was observed. CONCLUSIONS: The IL-1beta (-511) and (-31) polymorphisms were significantly associated with BP in women. The other genetic polymorphisms of cytokine genes that we analysed do not appear to be associated with BP susceptibility in our Chinese population.

A study on beams passing through hip prosthesis for pelvic radiation treatment.

PURPOSE: To study the dose distributions at the interface due to the presence of a metal implant; to show the dose distributions in combined fields in the presence of hip prostheses; and to demonstrate the capabilities and limitations of a conventional system. METHODS AND MATERIALS: Perturbations in the dose distribution caused by a hip prosthesis can result in unacceptable dose inhomogeneities within the target volume and in regions where tissues interface with implant. The Monte Carlo technique and a conventional treatment planning system are used to calculate the dose distributions. RESULTS: Dose increases of 15% in tissue are seen at the interface between metal implant and tissue. Dose reductions of 5-25% or 10-45% are observed in the shadow of the hip prosthesis made of 0.5-3-cm-thick titanium or steel alloy respectively. We compared predicted dose distribution between the Monte Carlo simulation and a commercial treatment planning system (CADPLAN). We found that CADPLAN underestimated the attenuation of hip prostheses. This has led to overestimation of the target dose by 14% for a typical four-field box technique. CONCLUSIONS: An acceptable dose distribution can be achieved with a proper lateral beam weighting and compensation using an eight-field technique. The beam compensation may be applied to achieve an adequate target dose.

Determination of percentage depth-dose curves for electron beams using different types of detectors.

According to the new AAPM TG-51 dosimetry protocol, reference dosimetry for electron beams is performed at depth of d(ref)=0.6R50-0.1 (cm) instead of d(max) recommended in TG-21. In clinical practice most electron beams are normalized at d(max). Therefore it becomes more important to get an accurate percentage-depth-dose (%dd) curve particularly for higher-energy electron beams in which the depth d(ref) is away from d(max). When ionization chambers are used in determining %dd curves the water-to-air stopping-power ratios and the fluence correction factors are required. The TG-51 recommends that the stopping-power ratios for realistic electron beams be used instead of the monoenergetic stopping-power ratios used in TG-21. This investigation aims to study the effects of those correction factors on the determination of %dd curves. We observed 1% deviations in the value of %dd at d(ref) for 15 and 18 MeV beams between a plane-parallel NACP and a cylindrical IC-10 chamber without considering the fluence correction factors P(fl). We explored a method to derive the fluence correction factors at any depth by using the existing fluence correction data at d(max) and tested its feasibility. We compared %dd curves measured by a diode detector and a NACP chamber with stopping-power ratios recommended by TG-51 and those recommended by TG-21. We found that for 15 and 18 MeV beams the difference in the values of %dd at d(ref) between using those two different stopping-power ratios is about 0.5%. Excellent agreement is found between %dd curves measured by the diode and by the NACP chamber when the stopping-power ratios recommended by TG-51 are used.

A longitudinal study of cardiac function in children with cancer over 40 months.

A previous study demonstrated impaired systolic function in 29% of patients treated with anthracycline as part of their therapy for malignant disease. A follow-up echocardiographic study was performed to determine whether there had been further deterioration of cardiac function. At least 40 months after the first study, those patients in whom abnormal systolic function had been detected and who had not received further anthracycline were studied by echocardiography using the same protocol as the initial study (group A). A second group of pediatric oncology patients who had not been given anthracycline but who had previously had cardiac assessment was selected as a control group (group N). The age and sex distributions of the two groups were comparable. Group A comprised 29 patients assessed on 2 occasions at mean times of 46 months and 89 months from the last dose of anthracycline. The mean dose of anthracycline received was 233 mg/m2 (range 20-400). Nine of 16 patients and 4 of 5 patients who had abnormal ejection fraction (EF) and fractional shortening (FS) at first assessment had normal EF and FS at the second assessment. There were no significant changes in EF, FS, and left ventricular wall stress (LVWS) between the two examinations. In group N, 20 patients were assessed after a mean interval of 43 months. There were no significant changes in EF, FS, or LVWS between the two examinations. At the first but not the second examination there were significant differences in the left ventricular internal diameters, EF, FS, and LVWS between group A and group N. Mildly abnormal cardiac indices detected in children after cessation of treatment with anthracycline did not deteriorate in 3 to 4 years follow-up. A longer cardiac follow-up study is indicated to assess the late outcome.

Cerebral blood flow during vasovagal syncope induced by active standing or head up tilt.

BACKGROUND: Vasovagal syncope is usually associated with a sudden drop of blood pressure and/or heart rate. However, occasionally the symptoms of syncope induced by orthostatic stress testing are not associated with obvious haemodynamic changes. The mechanisms of syncope in these patients are not clear. AIM: To evaluate changes in cerebral blood flow velocities during orthostatic stress testing in children and adolescents with vasovagal syncope. METHODS: Electrocardiogram, instantaneous arterial blood pressure, and right middle cerebral artery blood flow velocity were recorded at rest, during active standing, and 80 degrees head up tilt. 32 children and adolescents aged between 7 and 18 years with a history of repeated vasovagal syncope and 23 healthy control subjects were studied. RESULTS: Presyncope occurred in 10 patients during standing, and 13 patients during head up tilt. None of the controls had symptoms during the test. The transcranial Doppler study showed that the symptoms were associated with significant decreases of diastolic cerebral blood flow velocity and an increase of pulsatility. There was no significant change of the systolic cerebral blood flow velocity. The changes of cerebral blood flow velocities occurred in all episodes of presyncope, including those not associated with severe drop of blood pressure or heart rate. CONCLUSIONS: Diastolic cerebral blood flow velocity decreased significantly during episodes of presyncope induced by orthostatic stress. Impairment of autoregulation of cerebral blood flow might play an important role in the pathophysiology of syncope.

Transcription of metallothionein isoform promoters is differentially regulated in cadmium-sensitive and -resistant CHO cells.

Transcription regulation of metallothionein (MT) isoform promoters was investigated in Chinese hamster ovary (CHO) K1 and MT gene amplified, cadmium-resistant (CdR) cells. The transfected promoter of Chinese hamster MTI and MTII genes can be activated in both cell lines by stimulation with Cd or Zn ions, although no MT mRNA can be detected in CHO K1 cells after challenge with metal ions. Neither MT promoter used in this study can be activated by induction with dexamethasone, regardless of whether a sequence homologous to glucocorticoid responsive element is present. During induction by metal ions, differential promoter activities of the MT genes occurs in both CHO K1 and CdR cells where MTII promoter has a stronger activity than that of MTI. As indicated by a time course study in both cell lines, the relative induction ratios of both MTI and MTII promoters are similar at each time interval. This result is consistent with a differential transcriptional factor-promoter interaction for the two MT promoters. By using the CHO K1 and CdR cells as a model system, the occurrence of autoregulation for yeast CUP1 (MT) gene was examined in mammalian cells. Both MT promoters consistently show a lower basal activity but a higher induction ratio in CHO K1 than CdR cells; a result different from that of yeast CUP1 gene. When MTF-1 mRNA was examined, no difference in relative quantity was observed in CHO K1 and in CdR cells treated with metal ions or with metal ions absent.

N-hexane neuropathy in offset printers.

In an offset printing factory with 56 workers, 20 (36%) developed symptomatic peripheral neuropathy due to exposure to n-hexane. Another 26 workers (46%) were found to have subclinical neuropathy. The initial change in the nerve conduction study was reduced amplitude of the sensory action potentials, followed by reduced amplitude of the motor action potentials, reduction in motor conduction velocities and increase in distal latencies. These changes indicate primary axonal degeneration with secondary demyelination. Sural nerve biopsy in a severe case showed giant axonal swellings due to accumulation of 10nm neurofilaments, myelin sheath attenuation and widening of nodal gaps. The development of neuropathy bore no direct relationship to the duration of exposure, hence factors such as individual susceptibility may be important. Optic neuropathy and CNS involvement were uncommon and autonomic neuropathy was not encountered.

Surface hydrophobicity of gastric mucosa in peptic ulcer disease. Relationship to gastritis and Campylobacter pylori infection.

The hydrophobicity of biopsy specimens of gastric mucosa in 228 dyspeptic subjects undergoing diagnostic endoscopy was assessed by measuring the plateau-advancing contact angle of saline drops using a goniometer. Subjects with duodenal ulcers (n = 49) and gastric ulcers (n = 17) had significantly lower mean contact angles than controls (n = 124) without ulcer (57 degrees in duodenal ulcer, 59 degrees in gastric ulcer vs. 66 degrees in controls; p less than 0.0001). There was no change in contact angle after healing with H2-receptor antagonists by comparison with pretreatment (59 degrees vs. 56 degrees for duodenal ulcer, n = 15; 57 degrees vs. 59 degrees for gastric ulcer, n = 5). Controls with gastritis had lower contact angles than those without (61 degrees, n = 50, vs. 70 degrees, n = 63; p less than 0.0001). The presence of Campylobacter pylori was associated with a significant decrease in contact angle in controls (59 degrees, n = 39, vs. 70 degrees, n = 75; p less than 0.0001).

Specific terminal DNA replication sequence of X chromosomes in different tissues of a live-born triploid infant.

Using the thymidine pulse method, DNA replication kinetics were studied on cells derived from cartilage, gonad, lymphocytes, and skin of a live-born triploid (69,XXY) infant with typical clinical findings. Replication studies showed that 3% of the lymphocytes had one early and one late replicating X, and 97% of the lymphocytes, and cartilage, gonad, and skin cells had two early replicating X's. Asynchronous DNA replication between the two early replicating X's was observed in all tissues (range 25-40%). The predominant terminal replication sequence of X chromosomes from chondrocytes, gonad, and skin fibroblast differed from that of the lymphocytes. Thus, a tissue-specific DNA replication pattern of the early-replicating X chromosome may be present. In every tissue, the last band to complete DNA replication was Xq21. Polymorphisms of metaphase chromosomes of parents and the patient were studied by Q-banding. The possible origin of the extra haploid set of chromosomes is discussed.

Terminal deletion of the long arm of chromosome 4. Report of a case of 46, XY, del(4)(q31) and review of 4q- syndrome.

Using Q banding technique we recently identified a terminal deletion of the distal segment of the long arm of chromosome 4 in a male infant with multiple long arm of chromosome 4 in a male infant with multiple congenital anomalies. The breakpoint is at 4q31. The infant had hypertelorism, epicanthal folds, depressed nasal bridge, short nasal septum with upturned nose, bilateral open cleft lip and palate, retro- and micrognathia, low set, malformed ear, short neck, distally placed nipples, a sacral dimple, hypospadias, dysplastic nails, overriding toes, simian creases, patterns on interdigital and hypothenar areas, hypoplasia of gallbladder, and cardiac defects consisting of tricuspid atresia, left sided vena cava and anomalous aortic arch. This case is compared to the eight previously reported 4q- cases.