Jul 2026· Orphanet Journal of Rare Diseases· 0 citations
Medicine
TL;DR
Chinese SLS patients exhibit distinctive clinical and genetic patterns relative to other populations, with c.1157A > G being the most frequent variant andStructural modeling supports a potential conformational impact of these variants on FALDH.
Abstract
Objective
To characterize the clinical features and genetic spectrum of Chinese patients with Sjögren-Larsson syndrome (SLS).
Methods
We retrospectively reviewed genetically confirmed SLS cases managed in the Functional Neurosurgery Department of Beijing Children's Hospital. We also searched Chinese- and English-language databases to identify additional SLS cases for comparative analysis. Structural effects of detected variants on fatty aldehyde dehydrogenase (FALDH) were explored using PDB-derived models and PyMOL.
Results
Three SLS patients were identified, including one carrying a novel variant not previously reported. Literature review yielded 19 additional Chinese cases. Globally, SLS has a broad distribution, with the highest case counts reported in the United States, Sweden, and China. Compared with cohorts from other countries, Chinese patients showed a higher proportion of females, and compound heterozygous variants were more frequent than homozygous variants. The c.1157A > G substitution emerged as the most common variant in Chinese SLS. Three-dimensional modeling suggested that several variants likely perturb FALDH conformation.
Conclusion
Chinese SLS patients exhibit distinctive clinical and genetic patterns relative to other populations, with c.1157A > G being the most frequent variant. Structural modeling supports a potential conformational impact of these variants on FALDH.
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.
Renhua Wu, Lei Sun, Bao-Zhu Liu et al.· Zhonghua yi xue yi chuan xue...· 0 citations
It is shown that SQSTM1-associated ALS predominantly presents with limb onset, with a subset of patients exhibiting frontotemporal dementia or Paget’s disease, and its pathogenicity remains uncertain and requires further functional validation and pedigree confirmation.
Boyan Su, Ling Li, Xiaoxiao Zheng et al.· Neurogenetics· 0 citations
“hemiconvulsion-hemiplegia-epilepsy syndrome” is identified as a distinct feature and potential prognostic indicator for middle domain variants in DNM1L variants, which are predominantly missense, with the middle domain as a hotspot.
Han Xu, Chaolong Xu, Ying Zou et al.· Frontiers in Neurology· 0 citations
BACKGROUND
Pathogenic missense variants in the MORC2 gene are associated with two distinct disorders: Charcot-Marie-Tooth disease type 2Z (CMT2Z) and the recently described DIGFAN (developmental delay, impaired growth, dysmorphic facies and axonal neuropathy) phenotype, which encompasses a broad range of clinical manifestations that vary significantly between individuals.
METHODS
Clinical and imaging data from 16 patients were collected. Western blot analysis was performed on 10 identified variants in affected patients as well as on two novel variants without clinical data. Those missense variants were introduced into the wild-type vector transfected into HEK293T cells, and western blot analysis was performed to assess protein expression level.
RESULTS
A total of 11 different missense variants in the MORC2 gene were identified in our cohort, including four novel variants. We demonstrate that early-onset MORC2-associated disorders segregate into two principal neurological phenotypes: a predominantly neuromuscular form and a central nervous system-predominant form. The p.Ser87Leu variant, which defines the neuromuscular cluster, was uniquely characterised by a significant reduction in MORC2 protein levels, distinguishing it mechanistically from other variants. Overall, western blot analysis revealed no statistically significant difference in protein expression levels between variants related to CMT2Z and DIGFAN cases.
CONCLUSION
A comparison of our patients with previously reported cases revealed an intriguing trend suggesting a probable dependence of the leading clinical features on specific variants in the MORC2 gene. Further accumulation of patient data is required to determine whether this observation correlates with other specific variants.
A. Murtazina, Eugenii Tatarsky, I. Viakhireva et al.· Journal of Medical Genetics· 0 citations
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.
Ying Zhao, Yiyang Fu, Shuying Zhang et al.· Frontiers in Genetics· 0 citations
Confirming the underlying molecular etiology of hereditary hypophosphatemia (HH) to provide recurrence risk counseling is highly important. Our aims were to describe the detected variants and their distribution across Argentina and to contrast them with published data. Patients with HH prospectively referred to a hypophosphatemia program for genetic testing were included. Saliva samples were evaluated by next-generation sequencing with a panel of 13 genes associated with HH. In patients with no variants detected in the HH rickets related gene panel, multiplex ligation-dependent probe amplification was performed for the PHEX gene. Cascade genetic testing was recommended for at-risk relatives of index cases (IC). One hundred and sixty participants were enrolled, including 129 ICs with suspected HH (80.62%). Among them, 114 had a positive molecular test (88.37%); 93% were variations in the PHEX gene, predominantly single-nucleotide variants. Distribution of variant types was consistent with international databases. In our sample, 12% of subjects had undetectable variants in the gene panel, highlighting the importance of complete genome sequencing. Ours is the first study in Latin America to analyze PHEX variants, which is considered crucial for the generation of regional evidence to understand the genetic variability of HH and for leading specific targeted treatment.
S. Ávila, Sara Fernández, Maximiliano Zeballos et al.· American Journal of Medical...· 0 citations
