CCDC149: a novel gene associated with hypopituitarism and neurodevelopmental impairment.

Claudin-11-Mediated Hypomyelinating Leukodystrophy 22: New Insights Into Pathogenic Mechanisms.

CLDN11 has recently been associated with hypomyelinating leukodystrophy caused by de novo stop-loss variants. Here, we present a new case involving a homozygous variant in order to expand the genetic and clinical spectrum of the disease. We performed a comprehensive clinical, neuroradiological, and genetic evaluation in a child presenting with global developmental delay. Brain MRI and MR spectroscopy were obtained, and next-generation sequencing with parental segregation analysis was conducted. The patient presented with developmental delay, hypotonia, limb hypertonia, esotropia, and an absence of early developmental milestones in infancy, followed by partial motor improvement and persistent language and cognitive impairment. Brain MRI revealed diffuse supratentorial hypomyelination with stability over time. Genetic analysis identified a novel homozygous CLDN11 start-loss variant (c.1A>G; p.Met1Val), which is predicted to result in biallelic loss of function. Both parents were found to be heterozygous carriers. This case supports an autosomal recessive mechanism of CLDN11-related disease, which differs from the dominant stop-loss variants reported previously. The phenotype partially overlaps with that of earlier cases, but is characterized by milder motor involvement and more pronounced cognitive impairment. These findings broaden the mutational spectrum and suggest distinct pathogenic mechanisms, with important implications for diagnosis and genetic counselling.

3 EXOSC3 mutatiOns in POntOcerebellar hyPOPlasia tyPe 1: nOVel mutatiOns and genOtyPe-PhenOtyPe cOrrelatiOns

RFX3 Pathogenic Variants as a Rare Cause of Infantile Epileptic Spasms Syndrome

This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption, and highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders.

A Novel RNF216 Variant Causing Gordon Holmes Syndrome in Three Lithuanian Siblings

A novel homozygous missense variant in RNF216 gene c.1055T>G (p.(Phe352Cys)) in three siblings with Gordon Holmes syndrome is reported, contributing to the limited knowledge of GHS and highlighting the importance of hypogonadotropic hypogonadism treatment and close observation of neurological symptoms that may develop over time.

Biallelic EZH1 Nonsense Novel Variant in Two Siblings with Neurodevelopmental Disorder and Central Precocious Puberty: A Case Report from a Consanguineous Saudi Family

This study expands the clinical, genetic, and molecular spectrum of EZH1-associated neurodevelopmental disorders by demonstrating that reduced EZH1 expression is consistent with a loss-of-function disease mechanism.

Savelyeva LV. Isolated hypogonadotropic hypogonadism caused by a mutation in the WDR11 gene: a clinical case report

Isolated hypogonadotropic hypogonadism is a heterogeneous group of rare hereditary disorders characterized by impaired gonadotropin secretion, leading to delayed or absent puberty, reduced fertility, and infertility. In recent years, significant progress has been achieved in understanding the molecular genetic mechanisms underlying hypogonadotropic hypogonadism: more than 40 candidate genes have been identified, among which the WD‑repeat containing protein 11 ( WDR11 ) gene plays a key role. Advances in genetic diagnostics and the improvement of assisted reproductive technology (ART) programs expand the possibilities for personalized therapy in patients with hypogonadotropic hypogonadism. This paper presents two clinical cases of patients from the same family with hypogonadotropic hypogonadism caused by a mutation in the WDR11 gene, demonstrating different clinical manifestations and treatment strategies.