Aug 2026· Frontiers in Genetics· 0 citations· 31 references
TL;DR
A Chinese patient presenting with classic hallmarks of MGORS7 alongside atypical clinical features, including hearing and visual impairments is reported, suggesting that growth hormone therapy may be beneficial for growth retardation in patients with MGORS7.
Abstract
Meier-Gorlin syndrome 7 (MGORS7) is a rare autosomal recessive disorder characterized by primordial dwarfism, craniosynostosis, and patellar aplasia, caused by pathogenic variants of
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. Here, we report a Chinese patient presenting with classic hallmarks of MGORS7 alongside atypical clinical features, including hearing and visual impairments.
Clinical and radiological data were collected. Whole-genome sequencing and Sanger sequencing were performed to identify and validate the causative variants. Their functional effects were investigated using an exon-trapping assay, and a literature review of previously reported MGORS7 cases was conducted.
Genetic analysis identified two compound heterozygous
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variants: c.1416C>T (p.H472=) and c.1559+2T>A, which are a recurrent variant in the East Asian population and a novel variant, respectively. Our exon-trapping assay indicated that c.1559+2T>A induced aberrant splicing, generating transcripts predicted to undergo nonsense-mediated mRNA decay. Additionally, growth hormone therapy was initiated in our patient, with a noted improvement in growth parameters in the initial assessment and without immediate complications. The literature review identified a total of 32
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variants in 29 patients with MGORS7, who showed high heterogeneity in clinical phenotypes.
Our study further expanded the mutational spectrum of
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and provided a preliminary clinical observation suggesting that growth hormone therapy may be beneficial for growth retardation in patients with MGORS7.
INTRODUCTION
The Wnt ligand secretion mediator is encoded by WLS, and biallelic variants in this gene have been associated with an ultra-rare syndrome known as Zaki syndrome (ZKS). This study presents the fourteenth documented case of ZKS globally and reviews the clinical and genetic information of previously identified ZKS patients.
METHODS
A 17-year-old female from Iran underwent whole-exome sequencing due to a range of phenotypic symptoms suggestive of a unique syndrome. Sanger sequencing was employed to validate the candidate variant and to investigate its segregation among family members.
RESULTS
The patient was found to be homozygous for NM_024911.7: c.1433A>G, p.(Tyr478Cys) located in exon 11 of WLS. She represents the fifth ZKS patient identified with this variant, indicating a possible mutational hotspot. Furthermore, our patient exhibited distinct clinical characteristics compared to previously reported cases, including hyperphagia, congenital blindness, clinodactyly, and early pubertal development. A comparison of all reported ZKS patients suggests that this syndrome displays a recognizable pattern of developmental delay, intellectual disability, postnatal microcephaly, facial dysmorphism, skeletal and ocular anomalies, and short stature. Nevertheless, challenges persist in diagnosing ZKS due to poorly defined genotype-phenotype correlations.
CONCLUSION
The clinical characteristics observed in our patient expand the phenotypic spectrum of ZKS. Additionally, the p.(Tyr478Cys) variant may represent a potential mutational hotspot within WLS.
Naeim Ehtesham, M. Mazaheri, Zahra Sadr et al.· European Journal of Medical...· 0 citations
In this study, pathogenic FBN1 variants were identified in three patients, thereby confirming the clinical diagnosis of MFS and contributing two novel variants to the FBN1 variant repository, and provide a comparative assessment of genotype-phenotype correlations.
Xing Zhao, L. Yuan, Yan Sun et al.· Clinica chimica acta; intern...· 0 citations
Background Autosomal dominant polycystic kidney disease (ADPKD) is most commonly caused by pathogenic variants in PKD1. Here, we reported the functional characterization of an intronic PKD1 variant identified in an ADPKD-affected family and its subsequent application in preimplantation genetic testing for monogenic disorders (PGT-M). Case presentation A three-generation ADPKD family was enrolled. Whole-exome sequencing revealed a heterozygous PKD1 c.7489 + 5G>A variant, which co-segregated with the disease and was initially classified as a variant of uncertain significance. A minigene assay demonstrated that the variant induced skipping of exon 18, leading to a frameshift (p.Arg2404Valfs*123), supporting its reclassification as pathogenic. The couple underwent PGT-M using trophectoderm biopsy, haplotype linkage analysis, and direct mutation detection. An unaffected pregnancy was achieved, and subsequent prenatal diagnosis confirmed the absence of the variant and a normal chromosomal karyotype. Conclusion We validated a pathogenic splicing variant in PKD1 and successfully applied PGT-M to prevent disease transmission, resulting in an unaffected pregnancy.
Qiong Pan, Yuefang Liu, Xueping Sun et al.· Frontiers in Genetics· 0 citations
De novo variants of the WDR26 gene leading to haploinsufficiency have recently been associated with Skraban-Deardorff syndrome. The syndrome is an extremely rare autosomal dominant neurodevelopmental disorder that exhibits a wide range of clinical features including intellectual disability, delays in development, seizures, unusual facial characteristics, weak muscle tone, abnormal walking pattern, and multiple structural abnormalities. Here, we report a Chinese pediatric case of Skraban-Deardorff syndrome, wherein genetic testing revealed a novel de novo, heterozygous frameshift variant c.271delA (p.Thr91Profs*40) of the WDR26 gene. By reviewing previously reported cases, we found that dysfunction of the WDR26 gene does not necessarily accompany the occurrence of seizures. To date, epilepsy has not been a major symptom in any of the reported cases in China. Instead, delayed language development should be considered as the typical clinical phenotype of Skraban-Deardorff syndrome. It is worth noting that while epilepsy can be managed by medication, delayed language development does not have a straightforward treatment. If timely and adequate language interventional therapy and alternative communication methods are not implemented, the prognosis of children with Skraban-Deardorff syndrome may be significantly compromised.
Cuiyun Li, Ying Xu, Guiying Zhang et al.· Frontiers in Pediatrics· 0 citations
It is demonstrated that even in the absence of functional experiments, comprehensive family analysis can provide crucial clues for variant of uncertain significance (VUS) interpretation.
Xiulan Hao, Yanchou Ye, Man Liu et al.· Frontiers in Genetics· 0 citations