Retinitis pigmentosa (RP) is the most common form of hereditary retinal degenerative disease worldwide. We performed large-scale high-coverage targeted resequencing of 83 causative genes of RP. The analyzed samples accounted for more than 4 % of all RP patients in Japan, leading us to reveal comprehensive characteristics of causative genes and variants in the Japanese […]
Latest articles
Familial bilateral cryptorchidism is caused by recessive variants in RXFP2
Undescended testes or cryptorchidism is when one or both testes do not move down into the scrotum once developed. Found in 1.6 to 9.0% of boys, if left untreated, it can increase the risk of testicular cancer or infertility. We describe a family with four boys born with undescended testes. We identified a genetic change in […]
Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis
In this article, the authors test for enrichment of copy number variants (CNVs) at 55 well-characterized hotspots of recurrent copy number variation within a large cohort of isolated adolescent idiopathic scoliosis (AIS) patients. Of these 55 hotspots, only distal 16p11.2 duplications were enriched in AIS cases compared to control individuals. The authors replicated this finding […]
Pathogenic variants in PLOD3 result in a Stickler syndrome-like connective tissue disorder with vascular complications
Classification of rare, multisystemic connective tissue disorders (CTDs) can be difficult due to overlapping features with multiple CTDs and scarcity of clinical information. We describe 3 individuals in one family with a rarely reported autosomal recessive CTD due to pathogenic variants in PLOD3 that encodes the lysyl hydroxylase 3 enzyme, important for post-translational collagen modification. […]
Gastric cancer in Lynch syndrome is associated with underlying immune gastritis
The factors that predispose individuals with Lynch syndrome to gastric cancer are not well-described. In our cohort of 255 individuals with Lynch syndrome, chronic immune gastritis was observed in over 70% of the cases with gastric cancer and in none of the patients without gastric cancer. This suggests that chronic inflammation is an important risk […]
Homozygous mutations in SPEF2 induce multiple morphological abnormalities of the sperm flagella and male infertility
Male infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) is a genetically heterogeneous disorder. Previous studies revealed several MMAF-associated genes, which account for approximately 60% of human MMAF cases. The pathogenic mechanisms of MMAF remain to be illuminated. In this study, we identified SPEF2 as a novel gene for human MMAF across […]
Prenatal ultrasound findings of rasopathies in a cohort of 424 fetuses: update on genetic testing in the NGS era
In this study we describe the prenatal characteristics of Noonan syndrome and its associated syndromes called Rasopathies in 40 fetuses with a pathogenic variant in one of the Rasopathy genes. The most common feature is increased nuchal translucency (NT). Based on our data we suggest genetic testing of fetuses with an isolated persistent NT ≥5.0 […]
Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis
Congenital scoliosis (CS) is a common spinal anomaly and spondylo-costal dysostosis (SCDO) is a rare skeletal dysplasia affecting spine and rib. They have been considered to belong to different disease entities. We examined TBX6 in CS and SCDO and found loss-of-function (LOF) mutations in both. There were two LOF mechanisms: decreased transcriptional activity and mis-localization […]
Deciphering the complexity of the 4q and 10q subtelomeres by molecular combing in healthy individuals and patients with facio-scapulo-humeral dystrophy
Molecular diagnostics of FSHD remains complex for approximately 20% of patients, posing difficulties in genetic counseling. To overcome these current limitations, we have developed a molecular combing-based method allowing a precise bar coding of the 4q35 locus linked to the disease and 10qter region, which is highly homologous. By exploring a thousand cases with this […]
Mutation-specific Fabry disease patient-derived cell model to evaluate the amenability to chaperone therapy
Patients with Fabry disease (FD) and amenable mutations can be treated with the chaperone migalastat to restore endogenous α-galactosidase A (AGAL) activity. Our study demonstrates that repeated AGAL activity measurements in patients’ white blood cells at treatment-naïve baseline and during follow-up is mandatory to assess the in vivo amenability to migalastat. In addition, plasma lyso-globotriaosylceramide […]