Clinical Dysmorphology最新文献

Introduction: Biallelic variants in thiamine pyrophosphokinase 1 ( TPK1 ) are known to cause thiamine metabolism dysfunction syndrome 5 (THMD5). This disorder is characterized by neuroregression, ataxia and dystonia with basal ganglia abnormalities on neuroimaging. To date, 27 families have been reported with THMD5 due to variants in TPK1 .

Methods: We ascertained three individuals from three unrelated families. Singleton exome sequencing was performed on all three individuals, followed by in silico mutagenesis of the mutant TPK protein. Additionally, we reviewed the genotypic and phenotypic information of 27 previously reported individuals with THMD5.

Results: Singleton exome sequencing revealed a novel homozygous variant c.620A>T p.(Asp207Val) in TPK1 (NM_022445.4) in all three individuals. In silico mutagenesis of the mutant protein revealed a decrease in protein stability and altered interactions with its neighboring residues compared to the wild-type protein. Thus, based on strikingly similar clinical and radiological findings compared to the previously reported individuals and with the support of in silico mutagenesis findings, the above-mentioned variant appears to be the probable cause for the condition observed in the affected individuals in this study.

Conclusion: We report a novel homozygous variant in TPK1 , which appears to be recurrent among the Indian population.

Introduction: Neurodevelopmental disorders (NDDs) comprise conditions that emerge during the child's development and contribute significantly to global health and economic burdens. De novo variants in CNOT3 have been linked to NDDs and understanding the genotype-phenotype relationship between CNOT3 and NDDs will aid in improving diagnosis and management.

Methods: In this study, we report a case of a patient with CNOT3 -related NDD who presented with progressive aortic dilatation, a feature not reported previously.

Results: Our patient presented with intellectual disorder, dysmorphic facial features, and cardiac anomalies, notably progressive aortic dilatation - a novel finding in CNOT3 -related NDD. Genetic testing identified a de novo 6.3 kbp intragenic deletion in CNOT3 , providing a possible genetic basis for her condition.

Conclusion: This study presents the first case of CNOT3 -related NDD in Southeast Asia, expanding the phenotype to include progressive aortic dilatation and suggesting merit in cardiac surveillance of patients with CNOT3 -related NDD. It also emphasizes the importance of genetic testing in diagnosing complex NDD cases as well as reanalysis of 'negative' cases using advanced sequencing technologies to uncover potential hidden genetic etiologies in undiagnosed NDDs.

Objectives: Prader-Willi syndrome (PWS) is a rare and complex genetic disorder caused by the loss of expression of the paternal copy of the imprinted genes on chromosome 15q11-q13. A variety of findings have been reported on the phenotypic differences between the genetic subtypes of PWS. This article compares the clinical findings of 57 PWS patients by genetic subtype and explores possible associations in this context.

Methods: Methylation‑specific multiplex ligation-dependent probe amplification and single nucleotide polymorphism microarrays were used to diagnose deletion and uniparental disomy (UPD). For phenotype-genotype correlation, clinical data were collected and genetic subgroups were compared statistically, and P  < 0.05 was considered to indicate statistical significance.

Results: These 57 patients consisted of 15 type I deletions, 20 type II deletions, six atypic deletions, 11 heterodisomy UPD, four isodisomy UPD, and one translocation-type PWS. All patients had hypotonia, poor neonatal sucking, and feeding difficulties during infancy. Other PWS-related clinical findings, such as speech articulation problems (85.9%), sleep apnea (77.2%), normal birth length (71.9%), small hands/feet (71.9%), childhood polyphagia (57.9%), clinodactyly (56.1%), thick viscous saliva (54.4%), and behavioral problems (50.9%) were observed at varying rates with no statistical difference between genetic subtypes in general.

Conclusion: This study highlights the phenotype-genotype associations on PWS from a cohort of Turkish pediatric patients as a single-center experience.