Novel clinical and genetic findings in the present study contribute to a better understanding of the genotypic and phenotypic spectrum. Newly described cases with ultrarare phenotypes help achieve a clearer description of the clinical and genetic manifestations of the syndromes and gain a better understanding of the molecular mechanisms.

This study expands the POC1A-associated spectrum with four cases, detailing novel endocrine and dysmorphic features, dyslipidemia in the youngest SOFTS case, poor rhGH response, elevated IGF-1, and RNA impacts of two splice variants. A review of 43 cases highlights intellectual disability, craniocervical junction anomalies, and scoliosis, emphasizing comprehensive care needs.

This flow diagram summarized the study of 187 IDD patients from 140 families. Trio-WES was performed, followed by analysis of SNV/Indel and exon-based CNV. The results showed that 59.89% of the patients were not detected, 33.16% detected SNV/Indel, and 6.95% detected CNV. Validation was carried out using Sanger sequencing and/or CMA.

A schematic outlines CLMP gene variants linked to CSBS. Knocking down CLMP in zebrafish caused developmental defects, gastrointestinal motility disorders, and decreased smooth muscle gene expression.

Within a family, the cardiomyopathy phenotype is homogeneous in 96% of cases but the expressivity varies. Patients with predicted in-frame exon skipping presented DCM (84%), but a trend toward a lower rate of rhythmic disorders than TTNtv patients (0% vs. 29% respectively). We extended the genetic spectrum of TTNtv associated with DCM.

This is the first study to examine the clinical characteristics and molecular diagnosis of adult HCM patients from São Miguel Island. Novel variants and genotypes identified include large multi-exon deletions in MYBPC3, a homozygous missense variant in TNNT2, and a digenic heterozygous variant in TNNT2/MYH7.

This study describes the molecular investigation of 39 children with clinical suspicion of Silver-Russell syndrome at a tertiary center specialized in growth disorders. The results included differential diagnoses for 8 patients and underscore the importance of establishing a molecular diagnosis in this context to enable adequate management and genetic counseling.

We first reported a case of type XXII osteogenesis imperfecta caused by the homozygous c.492G > C (p. Leu164=) variant in the CCDC134 gene, which was identified by RNA sequencing analysis as an abnormal splicing variant causing deletion of Exon 5.

Split hand-foot malformation is a congenital limb malformation affecting primarily the central rays of the hands and/or feet, with variable expressivity, incomplete penetrance and syndromic forms. It is genetically heterogeneous, including point mutations and structural variants in different loci.

Five patterns of TEK variants (P1–P5) were identified from a retrospective review of 88 VM cases with a total of 107 clinically significant TEK variants. The correlation of clinical features among P1–P5 variant patterns was investigated from two different aspects: the malformation types and the affected anatomical locations.

Limb anomalies in eight families.

This paper reports two Lynch syndrome (LS) patients with mismatch repair proficient (MMRp) colorectal carcinomas (CRCs), challenging typical diagnostic methods reliant on MMR deficiency (MMRd) and microsatellite instability (MSI). It underscores the importance of comprehensive molecular testing, including germline analysis and reevaluation of MMR status in recurrent or metastatic CRCs.

Identification of a new pathogenic ASTN1 p.R517X (c.1549C>T) variant in a 7-month-old girl using gene sequencing methods and bioinformatics analysis.

Biallelic loss of function variant in SEC31A is associated with lethal neurodevelopmental disorder, dysmorphic features, and skeletal defects.

MLH3 is part of the MMR complex that is crucial for DNA repair. Recessive pathogenic variants in MLH3 causes polyposis-related cancer.