[A novel TPM1 variant causing Dilated cardiomyopathy in a child: A case report and literature review].

[Clinical characterization and genetic analysis of a patient with Fahr disease due to a homozygous variant of JAM2 gene].

The patient had developed unsteady gait 6 months before without clear cause, manifesting as a feeling of heaviness in the head and lightness in the feet, a sensation of walking on cotton wool when standing or walking, and the detection of the novel variant has enriched the mutational spectrum of the JAM2 gene.

Genetic analysis of childhood-onset dystonia-28 caused by a variant (c.5076G>A) in the KMT2B gene

The mutational spectrum of KMT2B is expands the mutational spectrum of KMT2B and provides additional evidence to support the genetic diagnosis and counseling of patients with KMT2B-related dystonia.

[Clinical manifestation and analysis of FBN1 gene variants in eight patients with Marfan syndrome].

Findings have enriched the mutational spectrum of the FBN1 gene among Chinese MFS patients and provided a basis for the genetic counseling and clinical management.

The Evaluation of Molecular Genetics and Clinical Manifestations in Patients With LZTR1-Associated Noonan Syndrome: A Retrospective Chart Review and Review of Literature.

Pathogenic variants in LZTR1 are an established cause of Noonan syndrome (NS) and uniquely exhibit both autosomal dominant (AD) and autosomal recessive (AR) inheritance. However, the phenotypic spectrum and genotype-phenotype correlations remain incompletely defined. We conducted a multi-center retrospective chart review of patients diagnosed with LZTR1-NS evaluated at three tertiary care centers. Clinical, molecular, and imaging data were systematically collected. A comprehensive literature review (2015-2025) identified 100 additional individuals meeting inclusion criteria. Comparative analyses were performed to evaluate phenotypic patterns by inheritance. Among 21 previously unreported patients aged 6 months to 49 years, 15 had AD NS and 6 had AR NS. Clinical features were largely consistent with prior reports, including high prevalence of craniofacial dysmorphism, neurodevelopmental and multisystem involvement. Cardiac manifestations were frequent, with pulmonary valve stenosis as the most common lesion. Hypertrophic cardiomyopathy appeared more prominent among AR NS. Notably, lymphatic abnormalities were observed at a higher frequency than previously reported. Compared to the literature, our cohort highlights novel findings, including the co-occurrence of AD LZTR1-NS with 22q11.2 deletion and two patients with AR NS with features suggestive of schwannomatosis. These findings expand the clinical spectrum of LZTR1-NS and have important implications for diagnosis, surveillance, and genetic counseling.

[Clinical phenotype and genetic analysis of a child with Basel-Vanagaite-Smirin-Yosef syndrome due to variant of MED25 gene].

Dilated cardiomyopathy with a MYH6 variant of uncertain significance (c.2894A > C, p.K965 T): a 13-year longitudinal follow-up case report

Background Genetic evaluation has become a routine component of clinical practice for dilated cardiomyopathy (DCM). However, a substantial proportion of test results return as variants of uncertain significance (VUS), posing considerable challenges for clinical decision-making and genetic counseling. The MYH6 gene encodes the cardiac α-myosin heavy chain, and although its association with DCM has been established, related case reports remain scarce, and the genotype–phenotype correlation is poorly defined. Case report We report a 41-year-old Han Chinese male carrying a heterozygous MYH6 variant (c.2894A > C, p.K965 T), classified as VUS in ClinVar, who presented with a progressive DCM phenotype. Despite 13 years of guideline-directed medical therapy, the patient demonstrated relentless left ventricular enlargement (left ventricular end-diastolic diameter increasing from 71 mm to 98 mm), persistent severe systolic dysfunction (left ventricular ejection fraction consistently ≤17%), and suffered an out-of-hospital cardiac arrest in the 12th year of his disease course. Cardiac magnetic resonance (CMR) revealed extensive transmural septal fibrosis. Sanger sequencing of family members showed that his healthy mother carried the identical variant, whereas his affected father and elder brother did not, forming a classic “genotype–phenotype non-segregation” paradox. Following the cardiac arrest, the patient received a cardiac resynchronization therapy defibrillator (CRT-D), but exhibited no left ventricular reverse remodeling at 12 months post-implantation and is currently undergoing pre-transplant evaluation for heart transplantation. Conclusion This case suggests that a MYH6 VUS may be associated with a severe and rapidly progressive DCM phenotype in specific clinical contexts. However, the non-segregation within the family implies that this variant may act merely as a disease modifier or may require synergistic genetic or environmental co-factors to manifest pathogenicity. Long-term multimodality imaging follow-up and assessment of device therapy response are critical for individualized management of VUS carriers.