Study on clinical features and diagnostic methods of prenatal Wolf-Hirschhorn syndrome / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical features of fetuses with Wolf-Hirschhorn syndrome(WHS) and explore the diagnostic methods and prenatal ultrasound characteristics and provide evidence for prenatal genetic counseling.@*METHODS@#We retrospectively analyzed 5 cases of WHS fetuses diagnosed from March 2016 to February 2020, and analyzed the results of chromosomal karyotype analysis and chromosomal microarray analysis (CMA) of the fetuses.@*RESULTS@#Five cases of WHS were detected by CMA, four cases were detected by karyotype analysis. Prenatal ultrasound revealed 4 abnormalities, of which 3 had intrauterine growth restriction, and only 1 had abnormalities of the maxillofacial region. The sequence of the fragments was 4p16.3p16.1 with a loss of 6.5 Mb, 4p16.3p15.32 with a loss of 15.6 Mb combined with 2p25.3 increased by 906kb, 4p16.3p15.31 with a loss of 20.4 Mb, 4p16.p15.1 with a loss of 35 Mb and 4p16.3p14 with a loss of 37 Mb.@*CONCLUSION@#Fetal growth restriction may be one of the early manifestations of WHS. Absence of fetal facial abnormality by prenatal ultrasound screening cannot exclude WHS. Karyotype analysis may miss the diagnosis of WHS, while combined CMA techniques can improve the diagnostic accuracy.

Clinical and Molecular Delineation of a Novel De Novo 4q28.3-31.21 Interstitial Deletion in a Patient with Developmental Delay

No abstract available.

Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight

The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candidate genes within linkage regions to identify genetic variants that predispose individuals to being overweight and developing type 2 diabetes. Through fine-mapping analysis of chromosome 4q34-35, we detected a locus potentially linked (nonparametric linkage 2.81, logarithm of odds 2.27, P=6 x 10-4) to type 2 diabetes in overweight or obese individuals (body mass index, BMI> or =23 kg m-2). Multiple regression analysis with type 2 diabetes-related phenotypes revealed a significant association (false discovery rate (FDR) P=0.006 for rs13144140; FDR P=0.002 for rs6830266) between GPM6A (rs13144140) and BMI and waist-hip ratio, and between NEIL3 (rs6830266) and insulin level from 1314 normal individuals. Our systematic search of genome-wide linkage and association studies, demonstrate that a linkage peak for type 2 diabetes on chromosome 4q34-35 contains two type 2 diabetes-related genes, GPM6A and NEIL3.

A familial deletion 4q syndrome: An outcome of a paracentric inversion.

Chromosome inversions are intra-chromosomal rearrangements formed when the chromosome breaks occur at two places, and in the process of repair the intervening segments are joined in an inverted or opposite manner. Inversions themselves do not appear to cause clinical anomalies, if balanced. Abnormal phenotypes can occur due to gene disruption at the point of breakage and reunion or due to duplication/deficiency recombinants formed during crossover at meiosis. We report a case with familial deletion 4q syndrome in a 1-year-old female child with dysmorphism and congenital abnormalities. The deletion was an outcome of a paracentric inversion 4q31.2q35.2. The deletion was confirmed by fluorescence in situ hybridization using telomeric DNA probes for chromosome No. 4. An attempt was made to correlate the genotype with the phenotype. The father had the same rearrangement with a milder phenotype. The recurrence risk in such cases is high.

Real-time quantitative PCR analysis of amplified DNA on chromosomes 4p15.2 and 6q23-24 from formalin-fixed, paraffin-embedded breast cancer tissues.

This study was performed to detect amplification of DNA sequences on chromosomes 4p15.2 and 6q23-24, obtained from formalin-fixed, paraffin-embedded, breast-cancer tissues. The prognostic relevance of the amplification was also demonstrated. DNA from formalin-fixed, paraffin-embedded tumor and corresponding normal tissues of 53 patients with breast cancer was extracted and amplified by real-time quantitative PCR technique. Amplification of the DNA sequences on chromosomes 4p15.2 and 6q23-24 was detected in 23 (43%) and 32 (60%) cases, respectively. Thirty-six (68%) cases showed amplification on both or one of the chromosomes. These frequencies are similar to that obtained from fresh samples in our previous study. In addition, amplification of the DNA on chromosomes 4p15.2 and / or 6q23-24 was predominantly observed in tumors with invasive ductal carcinoma. The findings in this study demonstrate that DNA extracted from formalin-fixed, paraffin-embedded breast tumors can be used to determine amplification of DNA sequences on selective chromosomal regions. We also suggest that the amplified DNA on chromosomal regions 4p15.2 and 6q23-24 might be involved in the development and progression of breast cancer.

Identification of Tumor Suppressor Loci on the Long Arm of Chromosome 4 in Primary Small Cell Lung Cancers

Recent cytogenetic studies have indicated that loss of the long arm of chromosome 4 is a frequent event in small cell lung cancer (SCLC), which suggests the presence of tumor suppressor genes there. To precisely map tumor-suppressor loci on chromosome 4q for further positional cloning efforts, we tested 15 primary SCLCs. Forty two polymorphic microsatellite markers located on chromosome 4q were used in the microsatellite analysis. We found that 12 (80%) of the 15 tumors exhibited loss of heterozygosity (LOH) in at least one of the tested microsatellite markers, and that 3 (25%) of these 12 tumors exhibited a larger area of deletion on chromosome 4q. Frequent LOH, defined as occurring in more than 50% of the tumors, was observed in five commonly deleted regions on 4q, namely 4q24, 4q27-28.3, 4q33, 4q34.1, and 4q34.3-35.2. Of these 5, LOH at 4q33 was the most frequent (61.5%). Six (40%) of the 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 3.7% (23 of 630) of the loci tested. Our data demonstrated that at least five tumor-suppressor loci exist on the long arm of chromosome 4 and that they may play an important role in the development and progression of primary small cell lung cancer tumorigenesis.

Asoción del síndrome de Wolf-Hirschhorn (deleción del brazo corto del cromosoma 4) con el síndrome de rubéola congénita / Association of the Wolf-Hirschhorn syndrome (deletion of the short arm at chromosome 4) with congenital rubella

Introducción. El síndrome de Wolf-Hirschhorn (SWH) es una cromosopatía poco frecuente, debido a la delección en la banda del brazo 4p16.3 que se manifiesta con una amplia variedad clínica, incluyendo malformaciones craneofaciales importantes. Caso clínico. Paciente de 3 mmeses de edad que acudió por presentar paladar hendido y que inició su manejo en el servicio de cirugía maxilofacial. Con el antecedente materno de haber presentado cuadro exantemático diagnósticado como rubéola durante el primer trimestre del embarazo. Se detectaron múltiples malformaciones congénitas agregadas (cardiovasculares, oftalmológicas y ortopédicas). Conclusiones. De acuerdo a los hallazgos fenotípicos se realizó el diagnóstico de SWH asociado a síndrome de rubéola congénita. Es éste el primer reporte en que se documenta la asociación de ambos síndromes