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Abstract Background Constitutional telomeric associations are very rare events and the mechanism underlying their development is not well understood. Case presentation We here describe a female case of Turner syndrome with a 45,X,add(22)(p11.2)[25]/45,X[5]. We reconfirmed this karyotype by FISH analysis as 45,X,dic(Y;22)(p11.3;p11.2)[28]/45,X[2].ish dic(Y;22)(SRY+,DYZ1+). A possible mechanism underlying this mosaicism was a loss of dic(Y;22) followed by a monosomy rescue of chromosome 22. However, SNP microarray analysis revealed no loss of heterozygosity (LOH) in chromosome 22, although a mosaic pattern of LOH was clearly detectable at the pseudoautosomal regions of the sex chromosomes. Conclusions Our results suggest that the separation of the dicentric chromosome at the junction resulted in a loss of chromosome Y without a loss of chromosome 22, leading to this patient’s unique mosaicism. Although telomere signals were not detected by FISH at the junction, it is likely that the original dic(Y;22) chromosome was generated by unstable telomeric associations. We propose a novel “pulled apart” mechanism as the process underlying this mosaicism.

Biallelic deletions extending into the ATPase family AAA-domain containing protein 3A (ATAD3A) gene lead to infantile lethality with severe pontocerebellar hypoplasia (PCH). However, only 12 such cases have been reported worldwide to date, and the genotype–phenotype correlations are not well understood. We describe cases associated with the same novel biallelic deletions of the ATAD3A and ATAD3B/3A regions in Japanese siblings with severe spinal cord hypoplasia and multiple malformations, including PCH, leading to neonatal death. The ATAD3A protein is essential for normal interaction between mitochondria and endoplasmic reticulum and is important for mitochondrial biosynthesis. The cases were evaluated using whole-genome sequencing for genetic diagnosis of mitochondrial disease. Spinal cord lesions associated with biallelic compound heterozygous deletion extending into the ATAD3A gene have not been reported. In addition, the ATAD3A deletion was 19 base pairs long, which is short compared with those reported previously. This deletion introduced a frameshift, resulting in a premature termination codon, and was expected to be a null allele. The pathological findings of the atrophic spinal cord showed gliosis and tissue destruction of the gray and white matter. We describe spinal cord lesions as a new central nervous system phenotype associated with a biallelic compound heterozygous deletion extending into the ATAD3A gene. Biallelic ATAD3A deletions should be considered in cases of mitochondrial disease with spinal cord hypoplasia and PCH.

Abstract Periodontal infection induces systemic inflammation; therefore, aggravating diabetes. Orally administered periodontal pathogens may directly alter the gut microbiota. We orally treated obese db/db diabetes mice using Porphyromonas gingivalis (Pg). We screened for Pg-specific peptides in the intestinal fecal specimens and examined whether Pg localization influenced the intestinal microbiota profile, in turn altering the levels of the gut metabolites. We evaluated whether the deterioration in fasting hyperglycemia was related to the changes in the intrahepatic glucose metabolism, using proteome and metabolome analyses. Oral Pg treatment aggravated both fasting and postprandial hyperglycemia (P

Glycogen storage disease type IV (GSD IV) is a rare inborn metabolic disorder characterized by the accumulation of amylopectin-like glycogen in the liver or other organs. The hepatic subtype may appear normal at birth but rapidly develops to liver cirrhosis in infancy. Liver pathological findings help diagnose the hepatic form of the disease, supported by analyses of enzyme activity and GBE1 gene variants. Pathology usually shows periodic acid-Schiff (PAS) positive hepatocytes resistant to diastase. We report two cases of hepatic GSD IV with pathology showing PAS positive hepatocytes that were mostly digested by diastase, which differ from past cases. Gene analysis was critical for the diagnosis. Both cases were found to have the same variants c.288delA (p.Gly97GlufsTer46) and c.1825G > A (p.Glu609Lys). These findings suggest that c.1825G > A variant might be a common variant in the non-progressive hepatic form of GSD IV.

Dandy-Walker malformation (DWM) is a posterior fossa anomaly characterized by hypoplasia and upward rotation of the cerebellar vermis and cystic dilation of the fourth ventricle. The cyst of DWM rarely extends posteriorly to almost completely fill the entire posterior fossa, which mimics primary cerebellar agenesis, a cerebellar porencephalic cyst, and an arachnoid cyst due to the lack of clarity of the thin cystic wall. A 10-month-old female born at 23 weeks’ gestation with cerebellar hemorrhage in the neonatal period was admitted to our hospital with dysphagia and side-to-side head bobbing. The detection of hemosiderin deposits enveloping the cyst wall by T2 star-weighted angiography (SWAN) was useful for the differential diagnosis of an acquired form of DWM from primary cerebellar agenesis. Cyst fenestration successfully improved dysphagia and head bobbing. A pathological specimen of the perforated cyst consisted of collagen fibers with hemosiderin deposits but lacked congenital cyst components. In infants with posterior fossa cysts, SWAN will be useful for a differential diagnosis between DWM and primary cerebellar agenesis.