[46,XY DSD induced by a novel mutation c.458T>C (p.Leu153Pro) of the LHCGR gene: A case report and review of the literature].

OBJECTIVE: To investigate the clinical characteristics and pathogenic basis of a case of 46, XY disorders of sex development (DSD) and analyze the relationship of the missense mutation with the phenotype of the LHCGR gene. METHODS: We analyzed the causative gene mutation by next-generation high-throughput sequencing (HTS) and confirmed it by Sanger sequencing. We detected the effect of the mutation on the splicing function by minigene assay, evaluated its pathogenicity using the ANNOVAR mutation annotation software, and analyzed the relationship of the missense mutation and the phenotype of the LHCGR gene via literature review and data mining. RESULTS: A homozygous mutation of C.458T>C (p.Leu153Pro) was detected in the last base of exon5 of the LHCGR gene in the 46,XY DSD patient, which was a new mutation not reported previously. The mother of the patient was a heterozygous carrier of the mutation. Minigene assay indicated that c.458T>C (p.Leu153Pro) did not affect the splicing function. The mutation was shown to be pathogenic by ANNOVAR software analysis and presumed inactive, possibly affecting its binding with the ligand and leading to type-I Leydig cell hypoplasia (LCH). Literature review and data mining showed that only 19 missense mutations could cause LCH, which scattered in the LHCGR gene. CONCLUSIONS: The new mutation c.458T> C (p.Leu153Pro) of the LHCGR gene found in the 46, XY DSD patient may cause LCH by interfering with the binding function of the ligand, which has enriched the LHCGR gene mutation database and provided some reference for the studies on the LCH genotype, its phenotypic correlation and gene functions.

Evaluation and comparison of three assays for molecular detection of spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is mainly caused by deletions in SMA-related genes. The objective of this study was to develop gene-dosage assays for diagnosing SMA. METHODS: A multiplex, quantitative PCR assay and a CNVplex assay were developed for determining the copy number of SMN1, SMN2, and NAIP. Reproducibility and specificity of the two assays were compared to a multiple ligation-dependent probe amplification (MLPA) assay. To evaluate reproducibility, 30 samples were analyzed three times using the three assays. A total of 317 samples were used to assess the specificity of the two assays. RESULTS: The multiplex quantitative PCR (qPCR) assay had higher reproducibility. Intra-assay CVs were 3.01%-8.52% and inter-assay CVs were 4.12%-6.24%. The CNVplex assay had ratios that were closer to expected (0.49-0.5 for one copy, 1.03-1.0 for two copies, and 1.50-1.50 for three copies). Diagnostic accuracy rates for the two assays were 100%. CONCLUSIONS: The multiplex qPCR assay was a simple, rapid, and cost-effective method for routine SMA diagnosis and carrier screening. The CNVplex assay could be used to detect SMAs with complicated gene structures. The assays were reliable and could be used as alternative methods for clinical diagnosis of SMA.

A Novel Case of 15q24 Microdeletion Syndrome Detected by MLPA in a Chinese Family.

BACKGROUND: Chromosome 15q24 microdeletion syndrome is a rare disease. To date, only 40 cases have been reported. Here, we also confirmed a 15q24 microdeletion syndrome in a chorionic villus of miscarriage. METHODS: The microdeletion was screened by multiplex ligation-dependent probe amplification (MLPA) and then identified by chromosomal microarray analysis (CMA). RESULTS: A 15q24 microdeletion syndrome was screened by MLPA in the chorionic villus of miscarriage in a Chinese family and was confirmed to be a de novo 3.143 Mb 15q24.1q24.2 deletion (chr15:72930195-76073450) by chromosomal microarray analysis (CMA). CONCLUSIONS: We first reported the 15q24 microdeletion syndrome screened by MLPA in Chinese population, and we also considered that the technique of MLPA with a suitable kit and probe could screen such a rare microdeletion quickly, economically, and efficiently.

[Two novel TSC2 frameshift mutations in tuberous sclerosis complex].

High-throughput sequencing was performed for the peripheral blood DNA from two probands in the family with tuberous sclerosis complex (TSC) to determine the sequences of TSC-related genes TSC1 and TSC2 and their splicing regions and identify mutation sites. Amplification primers were designed for the mutation sites and polymerase chain reaction and Sanger sequencing were used to verify the sequences of peripheral blood DNA from the probands and their parents. The two probands had c.3981-3982 insA (p.Asp1327AspfsX87) and c.4013-4014 delCA (p.Ser1338Cysfs) heterozygous mutations, respectively, in the TSC2 gene. The parents of proband 1 had no abnormalities at these two loci; the mother of proband 2 had c.4013-4014 delCA heterozygous mutation in the TSC2 gene, while the father and the grandparents of proband 2 had no abnormalities. c.3981-3982 insA mutation may cause early coding termination of amino acid sequence at the 1413th site, and c.4013-4014 delCA mutation may cause early coding termination of amino acid sequence at the 1412th site. These two mutations are the pathogenic mutations for families 1 and 2, respectively, and both of them are novel frameshift mutations, but their association with the disease needs to be further verified by mutant protein function cell model and animal model.

[Gene mutation analysis and prenatal diagnosis of four pedigrees with methymalonic aciduria].

OBJECTIVE: To study gene mutations in four pedigrees with methymalonic aciduria, as well as the feasibility of prenatal diagnosis of methymalonic aciduria. METHODS: High-throughput sequencing was performed for related genes in the peripheral blood of children or parents who were diagnosed with methymalonic aciduria to identify the loci with mutations. Then amplification primers were designed for each locus, and PCR and direct sequencing were performed to validate the sequencing in the first generation in the four pedigrees. Whether the mutations were pathogenic were determined with reference to literature review and medical history. In the pedigrees 1, 3, and 4, ultrasound-guided chorionic villi biopsy was performed at weeks 11-13 of pregnancy to perform early prenatal diagnosis. RESULTS: In pedigree 1, c.656A>T and c.729-730insTT heterozygous mutations in the MUT gene were detected in the proband's father and mother, respectively. Early prenatal diagnosis showed c.656A>T and c.729-730insTT double heterozygous mutations in the fetus. The couple decided to terminate pregnancy. In pedigree 2, c.1106G>A and c.755-756insA double heterozygous mutations in the MUT gene were detected in the proband. c.1106G>A came from the father and c.755-756insA came from the mother. In pedigree 3, c.217C>T and c.609G>A double heterozygous mutations in the MMACHC gene were detected in the proband. c.217C>T came from the father and c.609G>A came from the mother. Prenatal diagnosis showed c.609G>A heterozygous mutation in the fetus. The baby was successfully delivered, and the result of umbilical cord blood testing was consistent with the prenatal diagnosis. In pedigree 4, c.609G>A and c.567dupT double heterozygous mutations in the MMACHC gene were detected in the proband. c.609G>A came from the father and c.567dupT came from the mother. Prenatal diagnosis showed c.567dupT heterozygous mutation in the fetus. The baby was successfully delivered, and the result of umbilical cord blood testing was consistent with the prenatal diagnosis. CONCLUSIONS: Identification of gene mutations helps with prenatal diagnosis in pedigrees with methymalonic aciduria.

Molecular characterization and copy number of SMN1, SMN2 and NAIP in Chinese patients with spinal muscular atrophy and unrelated healthy controls.

BACKGROUND: Spinal muscular atrophy (SMA) is caused by SMN1 dysfunction, and the copy number of SMN2 and NAIP can modify the phenotype of SMA. The aim of this study was to analyze the copy numbers and gene structures of SMA-related genes in Chinese SMA patients and unrelated healthy controls. METHODS: Forty-two Chinese SMA patients and two hundred and twelve unrelated healthy Chinese individuals were enrolled in our study. The copy numbers and gene structures of SMA-related genes were measured by MLPA assay. RESULTS: We identified a homozygous deletion of SMN1 in exons 7 and 8 in 37 of 42 patients (88.1%); the other 5 SMA patients (11.9%) had a single copy of SMN1 exon 8. The proportions of the 212 unrelated healthy controls with different copy numbers for the normal SMN1 gene were 1 copy in 4 individuals (1.9%), 2 copies in 203 (95.7%) and 3 copies in 5 (2.4%). Three hybrid SMN genes and five genes that lack partial sequences were found in SMA patients and healthy controls. Distributions of copy numbers for normal SMN2 and NAIP were significantly different (P < 0.001) in people with and without SMA. CONCLUSION: The copy numbers and gene structures of SMA-related genes were different in Chinese SMA patients and healthy controls.

[Genetic and prenatal diagnosis for four families with Williams-Beuren syndrome].

Williams-Beuren syndrome is a common chromosome microdeletion syndrome. Early diagnosis and treatment are very helpful for patients and their families. This study identified the chromosome karyotype in one fetus with ultrasonography abnormalities and three children with developmental disorders from four families. This provided guidance for subsequent pregnancy and prenatal diagnosis by using routine G-banding chromosome karyotyping analysis, multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (array-CGH). In one amniotic fluid sample from a pregnant woman with fetal abnormalities on an ultrasound screen and three peripheral blood samples from three children with developmental disorders, the decreased signal of ELN gene probes at 7q11.23 and heterozygous deletions at 7q11.23 were detected by MLPA and array-CGH analysis. The laboratory genetic tests of amniotic fluid samples were normal when the mothers from the four families became pregnant again. It was concluded that MLPA and array-CGH are rapid and accurate tools for the diagnosis of Williams-Beuren syndrome and can provide more information for clinical genetic counseling.

[Analysis of copy number variations in an infant with Cri du Chat syndrome by array-based comparative genomic hybridization].

OBJECTIVE: To analyze genomic copy number variations in an infant with Cri du Chat syndrome, and to explore the underlying genetic cause. METHODS: G-banding analysis was carried out on cultured peripheral blood sample from the patient. Copy number variation analysis was performed using microarray comparative genomic hybridization, and the result was verified with fluorescence in situ hybridization. RESULTS: The infant was found to have a 46, XY, der(5) (p?) karyotype. By microarray comparative genomic hybridization, a 23.263 Mb deletion was detected in 5p14.2-p15.3 region in addition to a 14.602 Mb duplication in 12p31 region. A derivative chromosome was formed by rejoining of 12p31 region with the 5p14.2 breakpoint. The patient therefore has a karyotype of arr cgh 5p15.3p14.2 (PLEKHG4B>CDH12)× 1 pat, 12p13.33p13.1 (IQSEC3>GUC Y2C)× 3 pat. Loss of distal 5p and gain of distal 12p were verified with fluorescence in situ hybridization. CONCLUSION: The Cri du Chat syndrome manifested by the patient was caused by deletion of distal 5p from an unbalanced translocation involving chromosome 5. Microarray comparative genomic hybridization is a powerful tool for revealing genomic copy number variations for its high-resolution, high-throughput and high accuracy.

[Application of DHPLC screening TGFBR-3 gene in Chinese women with idiopathic premature ovarian failure].

OBJECTIVE: To evaluate clinical value of denaturing high performance liquid chromatography (DHPLC) used in detecting transforming growth factor beta receptor 3 (TGFBR-3) exons 11 and 12 polymorphism in women with idiopathic premature ovarian failure (POF). METHODS: From Feb. 2009 to Dec. 2011, 110 patients with idiopathic POF undergoing treatment at Shenzhen Maternal & Child Health Institute affiliated to Southern Medical University were enrolled as POF group in this study. In the mean time, 110 women under 40 years old with normal hormonal level and menstrual cycles as control group. The exons 11 and 12 of TGFBR-3 gene polymorphism were screened by using DHPLC, and results of DNA sequencing was as golden standard. Some related indexes were calculated, such as sensitivity, specificity, false negative value, false positive value, Youden index, positive predictive value, and negative predictive value. At the same time, 20% of the tested specimens were chosen randomly and detected by DHPLC again. The value of Kappa index were calculated by comparing the results between the first and second DHPLC analysis. RESULTS: The exon 11 of TGFBR-3 were not identified gene polymorphism and two nucleotide polymorphisms were identified in exon 12. For 2022 T/C polymorphism, the frequencies of CC with 0.9% (1/110), TC with 22.7% (25/110), TT with 76.4% (84/110), C with 12.3% (27/220) and T with 87.7% (193/220) in POF group were significantly different from CC with 0, TC with 9.1% (10/110) and TT with 90.9% (100/110), C with 4.5% (10/220) and T with 95.5% (210/220) in control group (all P<0.05). Allelic and genotypic frequencies of 2161-75 C/T were not differed significantly between the two groups (all P>0.05). As DNA sequencing as golden standard, DHPLC showed that the sensitivity was 100%, specificity was 97.9%, Youden index was 97.9%, positive predictive value was 96.3%, negative predictive value was 100%, and Kappa index was 0.888 (P<0.05). CONCLUSION: DHPLC analysis is higher validity, reliability and practicability method in detecting TGFBR-3 polymorphism in idiopathic premature ovarian failure.

[Cytogenetic and molecular analysis of idic(Yp) in 1 infertile man and 1 prenatal fetus].

OBJECTIVE: To evaluate idic(Yp) in genetic diagnosis by examining 1 infertile man and 1 prenatal fetus using cytogenetic and molecular techniques. METHODS: Following conventional chromosome preparation, we performed G- and C-banding karyo. typing and fluorescence in situ hybridization (FISH). Then we extracted genomic DNA using standard procedures and analyzed it by array-CGH and multiplex ligation-dependent probe amplification (MLPA). RESULTS: Both cases were diagnosed as 45, X/46, X, idic (Yp11.31) mosaicism. The man showed 2 intact copies of Yp11.31-q12 (chrY:2, 710, 250-57, 428, 567, SRY, ZFY, UTY and AZF), and the prenatal fetus exhibited similar findings except a paternal deletion in the AZFc region. CONCLUSION: idic(Y) (p11.31) causes short stature and male infertility. Array-CGH and MLPA can improve the accuracy of the diagnosis of 45, X/46, X, idic (Y) mosaicism, which may contribute to the studies of the phenotype-genotype correlation and clinical genetic counseling.

Emodin affects ERCC1 expression in breast cancer cells.

BACKGROUND: Multi-drug resistance to chemotherapeutic agents is a major cause of treatment failure in breast cancer. In this study, we investigated the effects of emodin on reversing the multi-drug resistance, examined the ERCC1 protein expression in breast cancer cell line, and explored the relationship between reversal of multi-drug resistance and ERCC1 protein expression. METHODS: MTT assay was conducted to test the cytotoxicity of adriamycin and cisplatin to MCF-7/Adr cells with and without emodin pretreatment, and Western blot was performed to examine the ERCC1 protein expression. RESULTS: MCF-7/Adr cells had 21-fold and 11-fold baseline resistances to adriamycin and cisplatin, respectively. When emodin was added to the cell culture at the concentration of 10 µg/ml, the drug resistance was reduced from 21 folds to 2.86 folds for adriamycin, and from 11 folds to 1.79 folds for cisplatin. MCF-7/Adr cells treated with two concentrations (10 µg/mL and 20 µg/mL) of emodin, after 2, 4, 6, 10 days, the trend of ERCC1 expression was gradually decreased and the reduction was more obvious comparatively at the concentration of 20 µg/mL. CONCLUSIONS: Emodin could reverse the multi-drug resistance in MCF-7/Adr cells and down-regulate ERCC1 protein expression.

FOXE1 polyalanine tract length screening by MLPA in idiopathic premature ovarian failure.

BACKGROUND: FOXE1 is one of the candidate genes for genetic predisposition to premature ovarian failure (POF) and it contains an alanine tract. Our purpose is to assess the influence of length of the alanine tract of FOXE1 on genetic susceptibility to POF. METHODS: The group studied consisted of 110 Chinese patients with idiopathic POF and 110 women from normal controls. The polyalanine tract and flanking sequence of FOXE1 was screened using the Multiple Ligation-dependent Probe Amplification (MLPA) technique and directly sequenced. RESULTS: Three variants of FOXE1-polyalanine length, containing 12, 14, or 16 alanine residues, and 5 different genotypes were identified. There were significantly lower frequencies of the 14/14 genotypes in cases with POF (X2 = 119.73, P = 0.001), as compared with the controls. The incidence of 16/16 genotypes of FOXE1-polyalanine was significantly higher in patients with POF (X2 = 3.403, P = 0.001) in comparison to the controls. The FOXE1 14 alanine allele was significantly less common in the POF patient group (186/220) than the controls (216/220) (X2 = 25.923, P = 0.0001). The FOXE1 16 alanine allele was significantly more common in the POF patient group (28/220) than the controls (4/220) (X2 = 19.412, P = 0.0001). CONCLUSION: This finding provides evidence that polyalanine repeat expansions in FOXE1 may be responsible for the genetic aetiology of POF in Chinese women.

Identification of novel missense mutations of the TGFBR3 gene in Chinese women with premature ovarian failure.

The aim of this study was to assess the association between human transforming growth factor ß receptor, type III (TGFBR3) and idiopathic premature ovarian failure (POF) in a Chinese population. A total of 112 Chinese women with idiopathic POF and 110 normal controls were examined. DNA samples prepared from blood leukocytes were used as templates for polymerase-chain reaction amplification of DNA fragments from TGFBR3. The gene fragments were sequenced. Web-based programs, including PolyPhen, Sorting Intolerant from Tolerant (SIFT), Prediction of Pathological Mutations (PMUT), ScanProsite and ClustalW2, were used to predict the potential functional and structural impacts of the missense variants of TGFBR3. A total of 11 novel variants were identified. Among them, six were found only in the POF patients. Two missense variants, p.E459G and p.P825L, which are conserved in primates, were predicted to have functional and structural impacts on the TGFBR3 protein. The other four variants (c.381+12A>C, c.2431-7A>G, p.S172S and p.C220C) were considered benign. However, further functional studies are necessary to confirm these findings.

[A novel mutation Glu441stop (GAA to TAA) of androgen receptor gene resulting in complete androgen insensitivity syndrome].

OBJECTIVE: To identify the mutation of human androgen receptor gene (AR) in a patient with complete androgen insensitivity syndrome (CAIS). METHODS: DNA sequences of 8 exons and their exon/intron boundaries of the AR gene in the patient were amplified by PCR and directly sequenced. RESULTS: DNA sequencing revealed a nonsense mutation in exon 1, resulting in a change of codon 441 GAA (glutamic acid) to a stop codon (TAA). CONCLUSION: A novel mutation Glu441stop (GAA to TAA) of the androgen receptor gene leading to complete androgen insensitivity syndrome was identified in this study in a Chinese patient. It may help us further understanding the pathogenesis of CAIS.

[Analysis of fetal chromosomal karyotype and etiology in 252 cases of early spontaneous abortion].

OBJECTIVE: To investigate the relationship between fetal chromosomal karyotype and early spontaneous abortion, and the effect of the environmental factors on spontaneous abortion. METHODS: Choronic villi from 252 cases of missed abortion were sampled as patient group and 50 normal pregnancies as control group. Chorionic villi were cultured and karyotype analysis was performed by G-banding. Clinical information was collected. RESULTS: The rate of chorion chromosome abnormality in the patient group was 58.09%, significantly higher than that in the control group (4.17%) (P<0.01). Among the 140 cases of karyotype abnormalities, 81 were trisomy, 29 were monosomy X and 17 were polyploidy, accounting for 57.86%, 20.71% and 12.14% of total abnormalities, respectively. Long time and low dose radiation exposure of the pregnant female seemed to be related with spontaneous abortion(P<0.01). CONCLUSION: Chorion chromosome abnormality is a major reason of early spontaneous abortion and karyotype analysis of chorionic villus is of clinical importance. For pregnant women, long-term exposure to computers and television seems a risk factor for missed abortion.

[Genetic analysis and prenatal diagnosis for a family with megalencephalic leukoencephalopathy and subcortical cysts].

OBJECTIVE: To identify potential mutation in the MLC1 gene in a Chinese family affected with megalencephalic leukoencephalopathy and subcortical cysts (MLC), and to provide prenatal diagnosis. METHODS: Genomic DNA of the patients, their parents and younger sister were extracted from peripheral blood. That of the fetus was extracted from an amniotic fluid sample. A total of 12 exons and at least 100 bp flanking the intronic sequence of the MLC1 gene were amplified with PCR. MLC1 mutations were screened by sequencing. Linkage analysis was performed for the family to assure accuracy of prenatal diagnosis. RESULTS: The two patients were both heterozygote for c.177_178delG (p.Ser60AlafsX5) mutation in exon 2 and c.598-2A>C change in intron 7. The c.177_178delG mutation was inherited from the father, and the c.598-2A>C mutation was inherited from the mother. The younger sister and the fetus have both inherited c.177_178delG from the father but did not inherit c.598-2A>C from the mother. Prenatal diagnosis suggested the fetus to be a carrier for a MLC1 mutation. Linkage analysis was consistent with the result of mutation detection. The fetus was born normal as predicted. CONCLUSION: The c.598-2A>C is a novel splicing mutation. Prenatal diagnosis through DNA sequencing and linkage analysis were performed for the first time on Chinese patients with MLC.

[Clinical significance of large-scale screening of A1555G mutation of mitochondria DNA for neonates].

OBJECTIVE: To explore the necessity of large-scale screening of mitochondria DNA (mtDNA) A1555G mutation for prevention of aminoglycoside antibiotic induced deafness in newborns. METHODS: One thousand blood filter samples were collected from neonates born in July 2008 in Shenzhen. DNA was extracted with Chelex-100 Resin and amplified by PCR. The mtDNA A1555G mutation was determined by denaturing high-performance liquid chromatography(DHPLC) for PCR products. The positive frequency was calculated. RESULTS: The mitochondrial DNA A1555G mutation was detected in 2 cases of 1000 neonates. The frequency of mutation was 0.2%. CONCLUSION: There is a high frequency of mtDNA A1555G mutation in neonates, the large-scale screening of mtDNAA1555G mutation in newborns might detect the individuals sensitive to aminoglycoside antibiotic, which is helpful to guide a rational medication for newborns and the maternal relatives at high-risk. Furthermore, it might be useful to prevent aminoglycoside antibiotic induced deafness.

[Karyotype analysis of chorionic villi from pregnant women with missed abortion using multiplex ligation-dependent probe amplification].

OBJECTIVE: To evaluate the clinical value of multiplex ligation-dependent probe amplification (MLPA) technique used in karyotype analysis of chorionic villi from missed abortion. METHODS: Feb 2008 to Oct 2008, 91 patients with missed abortion diagnosed by hormonal measurement, type B ultrasound and physical exam matched with 20 normal pregnant women undergoing artificial abortion were enrolled in this study. Chorionic villi was obtained by suction dilation and curettage in aseptic condition, then those villi was cultured and analyzed by traditional cytogenetic karyotyping method, in the mean time, the DNA extracted from villi was detected by MLPA. The results of chromosomal G-banding of chorionic villi were compared between two methods. RESULTS: The diagnostic concordance of MLPA and traditional karyotyping was observed in 92% (84/91) cases, there were 84 cases in the case group with diagnostic concordance by traditional karyotyping and MLPA except 7 cases of euploidy could not be detected by MLPA. The 84 cases included 40 normal karyotype, 29 trisomy of euchromosome, 1 double trisomy of euchromosome, 10 monosomy X, 1 monosomy X combined with trisomy of euchromosome, 2 chimaera of X chromosome, 1 structural abnormity of euchromosome. Among 7 cases with discordance diagnosis, 2 cases with trisomy and 5 cases with tetrasomy of euchromosome were identified in traditional karyotyping, however, they were all diagnosed with normal disomy by MLPA. Of 20 villi from normal pregnancy, two methods got the consistent results. CONCLUSION: The MLPA was rapid and efficacy method used for analyzing aneuploids in chorionic villi.

Maxillary Metastasis of Esophageal Cancer: Report of the First Case and Literature Review.

BACKGROUND: Esophageal cancer (EC) is a common digestive system tumor, characterized by high invasion, apparent lethality, and poor prognosis. Direct diffusion is the major metastatic mechanism of early EC, whereas advanced EC is spread mainly by lymphatic metastasis, but also can be transferred to the liver, lungs, bones, and so on, by hematogenous metastasis. The incidence of bone metastasis in esophageal cancer is low, and maxillary metastasis of EC is more rare. OBJECTIVE: To explore the differential diagnosis in ECMM, the rare metastasis of EC, and the possible mechanisms and predictors of bone metastasis. METHODS: The clinical materials of a male patient with maxillary metastasis of esophageal cancer (ECMM) were analyzed. Then, the possible mechanism of the ECMM was discussed. CONCLUSION: ECMM may belong to the hematogenous metastasis. The early detection of rare sites of metastasis of EC should be prioritized in tumor marker detection, imaging, pathology, and other diagnostic techniques.

[One case of 2q37 deletion syndrome: clinical and genetic diagnosis].

OBJECTIVE: To diagnose a new born baby with 2q37 deletion syndrome by comprehensive use of cytogenetic and molecular techniques and to investigate the phenotype characteristics and applicability of array-comparative genomic hybridization (array-CGH) and multiplex ligation-dependent probe amplification (MLPA) for detection of this syndrome. METHOD: Following conventional chromosome preparation, G banded karyotyping was performed.Genomic DNA was extracted using standard procedures, which were then analyzed by array-CGH and MLPA. RESULT: The patient presented with a typical face, special fist posture and congenital heart disease in 2q37 deletion syndrome. A 4.709 Mb deletion at 2q37.3 (chr2:237, 967, 852-242, 677, 269.NCBI36/hg18, including genes from COL6A3 toPDCD1) was detected by array-CGH. The results of MLPA and G banded karyotyping confirmed the existence of this deletion. CONCLUSION: 2q37.3 deletion was determined to be the cryptic cause of this case.2q37 deletion syndrome has some clinically recognizable characteristics. And array-CGH is a powerful technique for the accurate diagnosis and genotype-phenotype correlation study of this syndrome.