Identification of a submicroscopic 3.2 Mb chromosomal 16q12.2-13 deletion in a child with short stature, mild developmental delay, and craniofacial anomalies, by high-density oligonucleotide array-a recognizable syndrome.

Interstitial deletion of 16q has emerged into a recognizable pattern of congenital malformation. We report on a 9-year-old boy with short stature, psychomotor retardation, high forehead, broad flat nasal bridge, hypertelorism, cup-shaped ears, short neck, and a normal karyotype. Using high-density oligonucleotide array chip (Affymetrix 6.0) to perform parental and proband samples concurrently on three chips and interpreted as a trio set, a de novo 3.2 Mb deletion from bands q12.2 to q13 on chromosome 16 (from 52.08 to 55.3 Mb) of paternal origin was identified. The deletion was confirmed by quantitative genomic PCR and the break points were defined by junction PCR. Our study demonstrated the power of high-density oligonucleotide array chip in identifying novel submicroscopic deletions that were not detectable using G-banding cytogenetic technology. Furthermore, our result narrowed down the critical region for craniofacial features in interstitial 16q11.2-q13 deletion syndrome. In patients who have high forehead, broad flat nasal bridge, hypertelorism, cup-shaped ears, short neck and short stature, high-density array should be included in initial work up.

A genome-wide association study links small-vessel ischemic stroke to autophagy.

Genome-wide association studies (GWAS) can serve as strong evidence in correlating biological pathways with human diseases. Although ischemic stroke has been found to be associated with many biological pathways, the genetic mechanism of ischemic stroke is still unclear. Here, we performed GWAS for a major subtype of stroke-small-vessel occlusion (SVO)-to identify potential genetic factors contributing to ischemic stroke. GWAS were conducted on 342 individuals with SVO stroke and 1,731 controls from a Han Chinese population residing in Taiwan. The study was replicated in an independent Han Chinese population comprising an additional 188 SVO stroke cases and 1,265 controls. Three SNPs (rs2594966, rs2594973, rs4684776) clustered at 3p25.3 in ATG7 (encoding Autophagy Related 7), with P values between 2.52 × 10-6 and 3.59 × 10-6, were identified. Imputation analysis also supported the association between ATG7 and SVO stroke. To our knowledge, this is the first GWAS to link stroke and autophagy. ATG7, which has been implicated in autophagy, could provide novel insights into the genetic basis of ischemic stroke.

De novo MECP2 duplication derived from paternal germ line result in dysmorphism and developmental delay.

Xq28 duplications encompassing the methyl CpG binding protein 2 (MECP2) in males exhibit a distinct phenotype, including developmental delay, facial dysmorphism, muscular hypotonia, intellectual disability, poor or absent speech, recurrent infections and early death. The vast majority of affected males inherit the MECP2 duplication from their usually asymptomatic carrier mothers. Only a few cases with Xq28 duplication originating from de novo unbalanced X/Y translocation have been reported and the paternal origin of the aberration has only been validated in three males in the related literature. Here we present a karyotypically normal male with features characteristic of the MECP2 duplication syndrome. The genome-wide SNP genotyping shows a de novo 2.26-Mb duplication from Xq28 to the terminus. The genotypes of the SNPs within the duplicated region indicated a paternal origin. Furthermore, the results of fluorescence in situ hybridization (FISH) indicated a novel Xq:Yp translocation, characterized as der(Y)t(Y;X)(p11.32;q28), which suggests an aberrant that occurred during spermatogenesis. The phenotype is compared to the previously reported cases with Xq28 duplication originated from an unbalanced X/Y translocation, and there was no specific part of the phenotype that could be contributed to the origin of parental imbalances. This report further highlights the capacity of high-molecular cytogenetic methods, such as SNP array and FISH, in the identification of submicroscopic rearrangement, structural configuration and parental origin of aberrant while in the evaluation of children with idiopathic developmental delay and intellectual disability.

Endometriosis coexisting with dermoid cyst in a single ovary: a case report.

Endometriosis coexisting with a dermoid cyst of the ovary is extraordinarily rare, although both these benign conditions are said to be common in women in the reproductive age group. There are only two previous case reports,which is evident from our literature review from January 1960 through January 2010. Acute abdomen is one of the greatest diagnostic challenges and easily ignored by the clinicians to exclude the possibility of gynecologic illness. A 35-year-old woman was referred by the doctor in Family clinic. She experienced a three-day period of severe right lower abdominal pain and intermittent vomiting. Ultrasonography identified a bilocular, cystic, hypoechoic, and hyperechoic tumor, 7 cm × 6 cm × 6 cm in the right adnexal region. Laparoscopic cystectomy was performed under the impression of ovarian cyst with torsion or hemorrhage. The frozen section was benign and appendiceal status was adequate. Histopathologic examination described an ovarian cyst composed of endometrial-type lining with stromacells (endometriosis) and benign teratoma tissue with plenty of skin appendages and sebaceous glands. We report this unusual and interesting ovarian mass to remind physicians that the usage of the Endobag after cystectomy, the benefits on minimizing operative time, spilled opportunity, and postoperative complications. Laparoscopic techniques for large ovarian masses might be considered. The experience of the surgeon is also very important to prevent misdiagnosis or complication. Further follow up is mandatory for this simultaneous finding of ovarian endometriosis with coincidental dermoid cyst as a separate pathology in single ovary of such a nature. It also presents a challenge to the clinicians and to the pathologists.