Prenatal ultrasonography of craniofacial abnormalities

Craniofacial abnormalities are common. It is important to examine the fetal face and skull Epub ahead of print during prenatal ultrasound examinations because abnormalities of these structures may indicate the presence of other, more subtle anomalies, syndromes, chromosomal abnormalities, or even rarer conditions, such as infections or metabolic disorders. The prenatal diagnosis of craniofacial abnormalities remains difficult, especially in the first trimester. A systematic approach to the fetal skull and face can increase the detection rate. When an abnormality is found, it is important to perform a detailed scan to determine its severity and search for additional abnormalities. The use of 3-/4-dimensional ultrasound may be useful in the assessment of cleft palate and craniosynostosis. Fetal magnetic resonance imaging can facilitate the evaluation of the palate, micrognathia, cranial sutures, brain, and other fetal structures. Invasive prenatal diagnostic techniques are indicated to exclude chromosomal abnormalities. Molecular analysis for some syndromes is feasible if the family history is suggestive

Garip aileler

Fazlı Necip'in Yeni Asır'da tefrika edilen Garip Aileler adlı romanıArşivdeki eksikler nedeniyle tefrika yarım kalmıştır. Ancak tefrikanın tamamlandığı bilinmektedir

Copy number variation in Chinese patients with autism spectrum disorder

Introduction Although autism spectrum disorder (ASD) may have a multifactorial etiology, there is a strong genetic basis of the condition. With use of chromosomal microarray according to recommendation of international standards, copy number variations of uncertain significance (CNV VUS) are frequently found. The difficulty encountered in interpretation of CNV VUS may lead to challenges in genetic counselling and clinical management. In this study, we aim to study the CNV findings in Chinese children with ASD in Hong Kong, and to gather information with an aim to reclassify CNV VUS found in these children. Methods Patients with ASD of the department of Paediatrics QMH/HKU were recruited if their Array Comparative Genomic Hybridization (aCGH) were performed within the period from Jan 2011 to August 2014. Diagnosis of ASD was performed by developmental paediatricians and clinical psychologists using the Diagnostic and Statistical Manual of Mental Disorders, Fourth or Fifth Edition (DSM IV/V) criteria. The array was performed in Tsan Yuk Hospital Prenatal Diagnostic Laboratory (TYHPDL) using NimbleGen CGX-135k oligonucleotide array and Agilent CGX 60k oligonucleotide array. Array results were analyzed, information was gathered from the literature and existing databases with an aim to re-classify CNV VUS occurring in our ASD cohort. Results Among 288 patients with ASD in our cohort, 10 patients carried pathogenic or likely pathogenic CNVs (3.47%). Among the CNV VUS, we found that one CNV overlapping DPP10 (hg[19]chr2:116,534,689-116,672,358) was commonly occurring in TYHPDL database. The frequency of the CNV overlapping DPP10 in our ASD cohort was 0.35%; and 0.96% (9 from 935 individuals) in controls. The CNV was not statistically associated with ASD probands (P=0.467). The total frequency of the CNV overlapping DPP10 among all samples in TYHPDL was 1.01%. Similar CNVs were thought to be likely pathogenic in previous genetic study recruiting mainly Caucasians. However, there were individuals with typical development or not having ASD possessing similar CNVs in TYHPDL database as well as control databases focusing on Chinese population (9 in TYHPDL database, 1 in Singapore Genome Variation Project SGVP, 24 in The Singapore Prospective Study Program SP2). Conclusion Our study supported that the CNV overlapping DPP10 observed in our cohort may be more prevalent among Chinese and the study seemed to suggest that it was a CNV polymorphism among Hong Kong Chinese. This result would reclassify the CNV VUS to be likely benign in our locality. It also re-emphasized the need to account for ancestry and ethnicity for the precise interpretation of clinical microarray data.published_or_final_versionObstetrics and GynaecologyMasterMaster of Medical Science

Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10

Abstract Background Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. Methods DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. Results Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3′ exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. Conclusions The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings

Additional file 3: Table S3. of Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10

Indications of testing in non-ASD individuals with CNVs overlapping DPP10 in TYH database. (DOCX 15 kb