Human Genome Variation最新文献

Oculofaciocardiodental syndrome is caused by variants in the BCL6 corepressor (BCOR) gene. We identified a novel heterozygous frameshift variant, NM_001123385.2(BCOR):c.2326del, that arose de novo in a Japanese girl with characteristic facial features, congenital heart disease, bilateral syndactyly of toes 2 and 3, congenital cataracts, dental abnormalities, and mild intellectual disability. Reports of BCOR variants are rare, and further case accumulation is warranted.

Pathogenic variants of HECW2 have been reported in cases of neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL; OMIM #617268). A novel HECW2 variant (NM_001348768.2:c.4343 T > C,p.Leu1448Ser) was identified in an NDHSAL infant with severe cardiac comorbidities. The patient presented with fetal tachyarrhythmia and hydrops and was postnatally diagnosed with long QT syndrome. This study provides evidence that HECW2 pathogenic variants can cause long QT syndrome along with neurodevelopmental disorders.

Split-hand/foot malformation (SHFM) shows diverse heterogeneity and manifests with reduced penetrance and variable expressivity. This study investigated the underlying genetic cause of a family segregating SHFM. Exome sequencing followed by Sanger sequencing identified a novel single nucleotide heterozygous variant (NC_000019.9 (NM_005499.3):c.1118del) in UBA2 cosegregating in the family in an autosomal dominant manner. Our findings conclude that reduced penetrance and variable expressivity are the two remarkable and unusual features of SHFM.

Most variations in the human genome refer to single-nucleotide variation (SNV), small fragment insertions and deletions, and genomic copy number variation (CNV). Many human diseases including genetic disorders are associated with variations in the genome. These disorders are often difficult to be diagnosed because of their complex clinical conditions, therefore, an effective detection method is needed to facilitate clinical diagnosis and prevent birth defects. With the development of high-throughput sequencing technology, the method of targeted sequence capture chip has been extensively used owing to its high throughput, high accuracy, fast speed, and low cost. In this study, we designed a chip that potentially captured the coding region of 3043 genes associated with 4013 monogenic diseases, with an addition of 148 chromosomal abnormalities that can be identified by targeting specific regions. To assess the efficiency, a strategy of combining the BGISEQ500 sequencing platform with the designed chip was utilized to screen variants in 63 patients. Eventually, 67 disease-associated variants were found, 31 of which were novel. The results of the evaluation test also show that this combined strategy complies with the requirements of clinical testing and has proper clinical application value.

A 30-year-old male couple from Ardabil city, Iran, were admitted for premarital screening. An abnormal band in HbS/D regions with high levels of HbF and HbA 2 led us to suspect the possibility of a compound heterozygous state of β-thalassemia in our affected proband. Therefore, beta globin chain sequencing of proband discovered a heterozygote combination of the Hb G-Coushatta [b22 (B4) Glu>Ala, HBB: c.68A>C) with HBB: IVS-II-1 (G>A) mutation as a compound heterozygote.

Multiple bone disorders due to mutations in the human noggin (NOG) causes a variety of phenotypes. Hearing impairment due to stapes ankylosis secondary to bony degeneration is also a feature of these syndromes. We describe the case of an individual in a Japanese family with conductive hearing loss due to stapes ankylosis and hyperopia and dactylosymphysis. We revealed a novel NOG mutation, NM_005450.6:c.222 C > A / p.Tyr74*, and confirmed genetic significance.

Mutations in the neuroblastoma amplified sequence (NBAS) gene correlate with infantile acute liver failure (ALF). Herein, we identified a novel NBAS mutation in a female infant diagnosed with recurrent ALF. Whole-exome and Sanger sequencing revealed that the proband carried a compound heterozygous mutation (c.938_939delGC and c.1342 T > C in NBAS). NBAS c.938_939delGC was presumed to encode a truncated protein without normal function, whereas NBAS c.1342 T > C encoded NBAS harboring the conserved Cys448 residue mutated to Arg448 (p.C448R). The proportion of CD4 + T cells decreased in the patient's peripheral CD45 + cells, whereas that of CD8 + T cells increased. Moreover, upon transfecting the same amount of DNA expression vector (ectopic expression) encoding wild-type NBAS and p.C448R NBAS, the group transfected with the p.C448R NBAS-expressing vector expressed less NBAS mRNA and protein. Furthermore, ectopic expression of the same amount of p.C448R NBAS protein as the wild-type resulted in more intracellular reactive oxygen species and the induction of apoptosis and expression of marker proteins correlating with endoplasmic reticulum stress in more cultured cells. This study indicated that p.C448R NBAS has a function different from that of wild-type NBAS and that the p.C448R NBAS mutation potentially affects T-cell function and correlates with ALF.

Japan's government aims to promote the linkage of medical records, including medical genomic testing data and personal health records (PHRs), via cloud computing (the cloud). However, linking national medical records and using them for health care research can be controversial. Additionally, many ethical issues with using cloud networks with health care and genome data have been noted. However, no research has yet explored the Japanese public's opinions about their PHRs, including genome data, being shared for health care research or the use of the cloud for storing and analyzing such data. Therefore, we conducted a survey in March 2021 to clarify the public's attitudes toward sharing their PHRs, including genome data and using the cloud for health care research. We analyzed data to experimentally create digital health basic literacy scores (BLSs). Our results showed that the Japanese public had concerns about data sharing that overlapped with structural cloud computing issues. The effect of incentives on changes in participants' willingness to share data (WTSD) was limited. Instead, there could be a correlation between WTSD and BLSs. Finally, we argue that it is vital to consider not only researchers but also research participants as value cocreators in health care research conducted through the cloud to overcome both parties' vulnerability.

The N-terminus of the PRNP gene normally contains a 5-octapeptide repeat (R1-R2-R2-R3-R4), and insertions at this locus can cause hereditary prion diseases. In the present study, we found a 5-octapeptide repeat insertion (5-OPRI) in a sibling case of frontotemporal dementia. Consistent with previous literature, 5-OPRI rarely met the diagnostic criteria for Creutzfeldt‒Jakob disease (CJD). We propose 5-OPRI as a suspected causative mutation for early-onset dementia, especially the frontotemporal type.

We report a 1-year-old girl with congenital stromal corneal dystrophy confirmed by genetic analysis. The ocular phenotype included diffuse opacity over the corneal stroma bilaterally. We performed a genetic analysis to provide counseling to the parents regarding the recurrence rate. Whole exome sequencing was performed on her and her parents, and a novel de novo variant, NM_001920.5: c.953del, p.(Asn318Thrfs*10), in the DCN gene was identified in the patient.