Genetic mutation patterns in Indonesian children with primary steroid-resistant nephrotic syndrome.

A case report of WT1-associated infantile steroid-resistant nephrotic syndrome with atypical genotype–phenotype correlation

Infantile nephrotic syndrome (INS) has a slower progression to end-stage kidney disease (ESKD) than congenital nephrotic syndrome (CNS). The genetic variants are non-Finnish-type related; Denys-Drash syndrome (DDS) is the most frequent syndromic disease, characterized by a first-year onset of steroid-resistant nephrotic syndrome, disorder of sex development, predisposition to Wilms tumor, and diffuse mesangial sclerosis (DMS) in kidney biopsy. We report a previously healthy male infant with steroid-resistant nephrotic syndrome (SRNS), cryptorchidism, focal and segmental glomerular sclerosis (FSGS) with pseudo-cystic dilation of proximal tubules, initially interpreted as a genetic, non-syndromic nephrotic syndrome. A WT1 missense likely pathogenic variant was identified, then classified as incomplete Denys-Drash syndrome. We describe the phenotype of an unusual variant. The phenotypic heterogeneity of WT1-associated nephropathy can lead to a misdiagnosis, highlighting the importance of genetic testing in INS to achieve a correct diagnosis and provide the best treatment and surveillance according to the identified genetic variant.

[Clinical and genetic characteristics and genotype-phenotype correlations of pheochromocytoma and paraganglioma in children and adolescents].

PPGL in children and adolescents presents a strong hereditary predisposition; SDHB and VHL germline variants lead to distinctly divergent clinical phenotypes.

Whole-exome sequencing in pediatric drug-resistant epilepsy: diagnostic yield and clinical impact in a resource-limited setting

Genetic characteristics and clinical features of pediatric congenital adrenal hyperplasia in Korea

Genetics and clinical landscape of pediatric monogenic diabetes in consanguineous cohort: high diagnostic yield and recessive burden.

BACKGROUND Monogenic diabetes mellitus (MDM) comprises a heterogeneous group of rare disorders caused by single-gene defects. Data from highly consanguineous Middle Eastern populations remain scarce, which limits the application of precision medicine in these regions. OBJECTIVE To characterize the genetic spectrum, clinical features, and inheritance patterns of MDM within a large Saudi Arabian cohort. METHODS Exome sequencing (ES) and clinical analysis were conducted for 135 Saudi patients from 86 unrelated families. Variants were classified according to ACMG guidelines. RESULTS The cohort (52.6% male) exhibited a high consanguinity rate of 81%. A molecular diagnosis (Pathogenic/likely pathogenic) was achieved in 73% of families, with autosomal recessive inheritance predominating. Variant of uncertain significance (VUS) accounted for 15% of families. Leading clinical subtypes included MODY (33.3%), syndromic diabetes (27.4%), and permanent neonatal diabetes (23.7%). The most frequently implicated genes were INSR (13%), EIF2AK3 (12%), INS (11%), and GCK (11%). Furthermore, seven novel variants were identified. CONCLUSION MDM in Saudi Arabia is characterized by a high burden of autosomal recessive forms, including neonatal and syndromic diabetes, reflecting population structure and consanguinity. These findings highlight the importance of early genetic testing to guide management and genetic counseling.

Prognosis of pediatric hepatic Wilson disease with ATP7B loss of function variants

A single ATP7B LOF variant, especially c.813C>A was associated with advanced liver disease, portal hypertension, and extrahepatic involvement and over a follow-up of 6.7 years, a single LOF variant did not show a poorer liver or overall outcomes in comparison to ≥2 LOF variants.