Anomalies of the kidney and heart are the most commonly recognized congenital defects and constitute a major cause of morbidity in children. For example, STRING protein-protein interaction network for the hepatocyte nuclear factor 1-beta (HNF1B) gene with first-tier functional interactions involving detection of glucose and exocrine pancreas development with DNA and chromatin binding properties impacting transcription activity shows 10 nodes with 35 edges as illustrated affects development the kidney and urinary tract system. Network nodes represent proteins with splice isoforms or post-translational modifications collapsed into each node for all proteins produced by a single protein-coding gene. Edges represent protein-protein associations that are considered specific and meaningful, that is, proteins jointly contribute to a shared function. The HNF1B gene is the most known common cause of kidney and urinary tract defects accounting for 5%–31% of reported cases.

Four members of PPPs—PP1, PP2A, PP2B, and PP5—have been implicated in NDDs. And we reviews the genetic variants, clinical phenotypes, and pathogenic mechanisms associated with these four protein phosphatases.

We evaluated the genetic profile of prelingual patients affected by hearing loss. The findings revealed 10% frequency of GJB2 variants predominantly c.35delG. Exome sequencing identified the genetic causes of hearing loss in 70% of the patients. At least three founder alleles were identified.

ATP6V1B2 encodes the subunit of the vacuolar H⁺-ATPase, which is an enzyme responsible for the acidification of intracellular organelles. Animal model using Drosophila were generated to study the knock down effects of Vha55, which is the ATP6V1B2 ortholog in fly. The Vha55 knockdown flies show seizure-like behaviors and climbing defects. The study expands the variation spectrum of the ATP6V1B2 and suggested that the epilepsy phenotype can be attributed to ATP6V1B2 LOF.

MYBBBP1A pathogenic variants are associated with the development of hydrops fetalis under a predicted autosomal recessive pattern of inheritance. Most variants led to a truncated protein and immunohistochemistry confirmed the differential pattern of expression of fetuses with HF compared to non-HF age and sex matched control.

This study represents the largest CTX case series ever reported in South America. We report three new pathogenic or likely pathogenic variants and describe phenotypic characteristics. The age of walking aid need seems to be much closer to the onset of neurological symptoms than to the disease presentation itself.

The epidemiological study of 1351 Chinese patients with mitochondrial disease reveals that the most prevalent phenotypes are mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), chronic progressive external ophthalmoplegia (CPEO), and Leigh syndrome. Additionally, the study identified several rare phenotypes. The primary genetic cause is mitochondrial DNA mutations.

A pre-school boy with a de novo novel MT-TD variant m.7560T>C presented with steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis characterized by podocyte mitochondrial abnormalities, cortical blindness, pancreatitis, seizures, lactic acidemia, and brain magnetic resonance imaging abnormalities. This discovery expands the phenotypic and mutational spectrum of primary mitochondrial diseases.

Minigene analysis, RT-PCR and Quantitative Real-time PCR (RT-qPCR) confirmed that all 7 variants identified by Whole-exome sequencing (WES) from 5 patients afflicted with reproductive genetic disorders can cause aberrant splicing, with 6 variants significantly altering mRNA levels.

We describe two affected individuals with arthrogryposis multiplex congenita-4 with SCYL2 bi-allelic loss-of-function variants, and two individuals homozygous for SCYL2 missense variants presenting with developmental delay only. Our study confirms the association of SCYL2 with arthrogryposis multiplex congenita-4 and suggests a milder phenotype can occur.

This study introduces a novel, synonymous variant in CASK that disrupts a donor splice-site in exon 18, in a male patient with MICPCH. Lymphocyte transcriptomics identified 12 CASK transcripts secondary to the variant; 32% were predicted to undergo nonsense-mediated decay, and 99% skipped exon 18, altering the PDZ domain.

Plectin, a cytoskeletal linker of intermediate filaments encoded by the PLEC gene, has been implicated in cholestatic jaundice in two unrelated infants with novel PLEC variants. Immunofluorescence staining of liver tissue in these cases mirrored findings from the first two reported cases, reinforcing the role of plectin in cholestasis.

We report two fetal cases of glutathione synthetase deficit, presenting with a severe polymalformative syndrome including limb anomalies. Both fetuses are compound heterozygous for two GSS variants: an out-of-frame deletion of the exon 3 and a reported missense substitution. 5-oxoproline levels in amniotic fluid were elevated.

All reported ABL1 gain of function and loss of function (LOF) variants, impact both isoforms 1a and 1b. Our findings suggest that LOF variants affecting solely ABL1 isoform 1b may lead to a distinct autosomal recessive new phenotype.

In the present case, we report two sisters with Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS), a novel nonsense mutation (c.169C > T, NM_005654.5) in the NR2F1 gene and potential gonadal mosaicism as the cause of this rare disease, making it the second such case described in the literature.