OBJECTIVE: To explore the genetic basis for a fetus with club foot detected upon mid-pregnancy ultrasonography. METHODS: Amniotic fluid of the fetus and peripheral blood samples of its parents were collected and subjected to G-banding karyotype analysis and copy number variation sequencing (CNV-seq). The result was verified by fluorescence in situ hybridization (FISH). RESULTS: The fetus and its parents all had a normal karyotype. CNV-seq analysis revealed that the fetus has harbored a 23.12 Mb on chromosome 5 and a 21.46 Mb duplication on chromosome 7. FISH assay has verified that its mother has carried a cryptic t(5;7)(p14.3;q33) translocation. CONCLUSION CNV-seq combined with FISH can effectively detect cryptic chromosome aberrations, and can help to reduce severe birth defects and provide a basis for prenatal genetic counseling.
Pregnancy ; Female ; Humans ; Cri-du-Chat Syndrome ; In Situ Hybridization, Fluorescence ; DNA Copy Number Variations ; Prenatal Diagnosis ; Fetus ; Amniotic Fluid ; Chromosome Deletion

A premature infant with gestational age 36⁺⁴ weeks was admitted with respiratory distress syndrome. Surfactant and ventilation were firstly done to improve his respiration. After extubation, weak, high-pitched cry and asymmetric face with micrognathia and hypertelorism were detected. Therefore, cytogenetic analysis was performed, and his karyotype was 46, XY, del(5) (p14p15.33). Pontine hypoplasia was detected on cranial magnetic resonance imaging (MRI). Therefore, karyotyping and cranial MRI should be performed in case of preterm infants with suspicion of Cri-du-chat syndrome (CdCS).
Cri-du-Chat Syndrome* ; Cytogenetic Analysis ; Gestational Age ; Humans ; Hypertelorism ; Infant, Newborn ; Infant, Premature* ; Karyotype ; Karyotyping ; Magnetic Resonance Imaging ; Micrognathism ; Pons ; Respiration ; Ventilation

OBJECTIVETo use combined G-banding and array-comparative genomic hybridization (aCGH) for the prenatal diagnosis of a fetus with 5q35 deletion syndrome.

METHODSChromosomal karotypes of the fetus and parents were analyzed with G-banding analysis. aCGH was performed to detect minor chromosomal structural abnormalities.

RESULTSThe karyotype of the fetus was ascertained as 46, XY, t(5;10)(q35;p13), and the karyotypes of the parents were normal. aCGH has identified a de novo 1.68 Mb deletion at 5q35.2q35.3 and a 1.44 Mb duplication at 10p14p13.

CONCLUSIONaCGH has a higher resolution and greater accuracy for mapping chromosomal aberrations and is a useful supplement for G banding karyptyping analysis.

Adult ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; genetics ; Comparative Genomic Hybridization ; Cri-du-Chat Syndrome ; diagnosis ; embryology ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Karyotyping ; Male ; Prenatal Diagnosis ; Trisomy ; diagnosis ; genetics

5p deletion syndrome, also known as Cri-du-Chat syndrome, is a chromosomal abnormality caused by a deletion in the short arm of chromosome 5. Clinical features of 5p deletion syndrome are difficult to identify prenatally by ultrasound examination, thus most cases of 5p deletion syndrome have been diagnosed postnatally. Here, we report eight cases of 5p deletion syndrome diagnosed prenatally, but were unable to find common prenatal ultrasound findings among these cases. However, we found that several cases of 5p deletion syndrome were confirmed prenatally when karyotyping was performed on the basis of abnormal findings in a prenatal ultrasound scan. Hence, it is necessary to carefully perform prenatal ultrasonography for detection of rarer chromosomal abnormalities as well as common aneuploidy.
Aneuploidy ; Arm ; Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; Cri-du-Chat Syndrome* ; Karyotyping ; Prenatal Diagnosis* ; Ultrasonography ; Ultrasonography, Prenatal

OBJECTIVETo establish a nested case-control study cohort in myelodysplastic syndrome (MDS) patients and investigate the clinical characteristics, WHO subtype and risk factors associated with MDS evolution to leukemia of this cohort.

METHODSAll patients, ≥18 years of age, provided by 24 Shanghai hospitals with initial clinical findings consistent with a hematopoietic abnormality between June 2003 and April 2007, were the candidates for inclusion in this study. The blood and bone marrow samples of every patient should be provided at baseline. Diagnosis was made by incorporating morphologic, immunophenotypic, cytogenetic and molecular features according to WHO classification criteria. Cytogenetic analysis was performed using conventional G-banding karyotyping and fluorescence in situ hybridization (FISH) techniques. Cumulative risk of evolution was estimated by Kaplan-Meier method. Prognostic factors were evaluated by univariate Log-rank method and multivariate Cox proportional hazard models.

RESULTSA total of 435 patients were diagnosed as MDS. The median age of MDS onset was 58(18-90) years, with 248 male patients and 187 female patients (male: female 1.33: 1). The percentage of cases with refractory cytopenia with multilineage dysplasia (RCMD) was the highest (65.5%), while that of refraetory anemia (RA) (2.3%), refractory anenia with ring sideroblast (RARS) (1.1%) and 5q-syndrome (0.5%) was lower. Trisomy 8 (+8) was the most common chromosome abnormalities (71 cases, 12.7%). The mean follow-up time was 20.3 (4.2-57.1) months. Cases were patients with evolution by the end of follow-up, while controls were patients without evolution by that time. Case group included 41 patients and control group included 342 patients. Univariate analysis showed that the age, sex, WHO subtype, WBC count, absolute neutrophil count (ANC), IPSS cytogenetic subgroup, IPSS group and bone marrow blast percentage were significant risk factors for leukemia-free survival (LFS). Multivariate analysis of COX model showed that the age, sex, WHO subtype, IPSS cytogenetic subgroup and bone marrow blast were independent risk factors for LFS.

CONCLUSIONA nested case-control study cohort of MDS patients is established. The clinical characteristics and WHO subtype of MDS patients in Chinese Shanghai are different from that in Western countries. The independent risk factors for MDS evolution are age, sex, WHO subtype, IPSS cytogenetic subgroup and bone marrow blast percentage.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Bone Marrow ; Case-Control Studies ; China ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; Chromosomes, Human, Pair 8 ; Cri-du-Chat Syndrome ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia ; Male ; Middle Aged ; Myelodysplastic Syndromes ; Proportional Hazards Models ; Risk Factors ; Trisomy ; Young Adult

A 21-month-old girl with cri-du-chat syndrome in conjunction with developmental delay underwent brain magnetic resonance imaging (MRI). The MRI showed hypoplasia of the brain stem, a normal cerebellum, thinning of the corpus callosum, and a lack of myelination in both anterior limbs of the internal capsule. She also had neonatal bilateral subependymal cysts. We believe that the symmetrical lack of myelination in both anterior limbs of the internal capsule could be a diagnostic clue of cri-du-chat syndrome.
Brain ; Brain Stem ; Cerebellum ; Corpus Callosum ; Cri-du-Chat Syndrome* ; Extremities* ; Female ; Humans ; Infant ; Internal Capsule* ; Magnetic Resonance Imaging ; Myelin Sheath*

OBJECTIVETo diagnose a neonate presenting with multiple dysmorphic features, Cri-du-chat signs and hypoglycemia and to correlate the phenotype with the genotype.

METHODSThe patient was diagnosed with conventional cytogenetics and real-time fluorescence quantitative PCR (QF-PCR). The phenotype was then correlated with the genotype through a review of literature.

RESULTSThe neonate was diagnosed with a partial 13q trisomy (q12 → qter) and partial 5p monosomy (p15 →pter).

CONCLUSIONA rare diagnosis has been established with combined cytogenetic and molecular genetic techniques. QF-PCR has a broad application in genetic diagnosis.

Chromosomes, Human, Pair 13 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Cri-du-Chat Syndrome ; diagnosis ; genetics ; Cytogenetics ; Female ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; diagnosis ; genetics ; Male ; Trisomy ; diagnosis ; genetics

Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.
Brain Stem/*pathology ; Cri-du-Chat Syndrome/*complications/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Infant ; Magnetic Resonance Imaging/*methods ; Pons/pathology

OBJECTIVETo analyze genomic copy number variations in an infant with Cri du Chat syndrome, and to explore the underlying genetic cause.

METHODSG-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.

RESULTSThe 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.

CONCLUSIONThe 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.

Adult ; Chromosome Banding ; Chromosome Deletion ; Comparative Genomic Hybridization ; Cri-du-Chat Syndrome ; genetics ; DNA Copy Number Variations ; Female ; Humans ; Infant ; Male

OBJECTIVETo determine the karyotype of a boy suspected to have Cri du Chat syndrome with severe clinical manifestations, and to assess the recurrence risk for his family.

METHODSHigh-resolution GTG banding was performed to analyze the patient and his parents. Fluorescence in situ hybridization (FISH) with Cri du Chat syndrome region probe as well as subregional probes mapped to 5pter, 5qter, 18pter, 18qter, and whole chromosome painting probe 18 was performed to analyze the patient and his parents. In addition, single nucleotide polymorphism-based arrays (SNP-Array) analysis with Affymetrix GeneChip Genome-wide Human SNP Nsp/Sty 6.0 were also performed to analyze the patient.

RESULTSKaryotype analysis indicated that the patient has carried a terminal deletion in 5p. FISH with Cri du Chat syndrome region probe confirmed that D5S23 and D5S721 loci are deleted. SNP-Array has detected a 15 Mb deletion at 5p and a 2 Mb duplication at 18p. FISH with 5p subtelomeric probes and 18p subtelomeric probe further confirmed that the derivative chromosome 5 has derived from a translocation between 5p and 18p, which has given rise to a 46,XY,der(5)t(5;18)(p15.1;p11.31)dn karyotype.

CONCLUSIONA de novo 5p partial deletion in conjunction with a cryptic 18p duplication has been detected in a boy featuring Cri-du-Chat syndrome. His parents, both with negative findings, have a low recurrence risk. For its ability to detect chromosomal imbalance, SNP-Array has a great value for counseling of similar patients and assessment of recurrence risks.

Child, Preschool ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 18 ; Chromosomes, Human, Pair 5 ; Cri-du-Chat Syndrome ; diagnosis ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Phenotype ; Polymorphism, Single Nucleotide ; Trisomy