OBJECTIVE: To explore the clinical features and genetic etiology of a child with Hoyeraal-Hreidarsson syndrome (HHS). METHODS: A child with HHS diagnosed at the Affiliated Hospital of Jining Medical University due to "developmental delay and anaemia" on April 27, 2024 was selected as the study subject. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members. Whole-exome sequencing was carried out, and candidate variant was verified by Sanger sequencing of his family members and bioinformatics analysis using CASAVA v1.8.2. The pathogenicity of the candidate variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by the American College of Medical Genetics and Genomics (ACMG). Relevant literature on HHS cases reported in China was reviewed to analyze the clinical and genetic characteristics. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-10-C003). RESULTS: The child, a 7-month-old boy, had mainly manifested with growth retardation, developmental delay, microcephaly, cerebellar hypoplasia, immunodeficiency and bone marrow failure. Routine blood test indicated pancytopenia. The immunological workup showed reduction of B cells, NK cells and immunoglobulins. Cranial MRI demonstrated the volume of bilateral cerebellar hemispheres and brainstem and corpus callosum was small. Whole-exome sequencing revealed that he has harbored a hemizygous c.103_105del (p.Glu35del) variant of the DKC1 gene. Sanger sequencing showed that his mother and two sisters have carried the same variant. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PM1+PM4+PS4_Supporting+PM2_Supporting). Four relevant literature were retrieved, which has involved 8 HHS cases. Together with the patient from this study, they have consisted of 8 males and 1 females. The most common symptoms of the 9 patients were blood system abnormalities and developmental delay. All patients had shown cerebellar dysplasia and anemia/erythrocytopenia. Among them, 3 cases have harbored TINF2 gene variants, and 6 cases had harbored DKC1 gene variants. The c.103_105del variant has not been reported in China previously. CONCLUSION The hemizygous c.103_105del (p.Glu35del) variant of the DKC1 gene probably underlay the disease in this child. Above finding has expanded the mutational and phenotypic spectra of the DKC1 gene, and has facilitated early diagnosis of HHS in this child.
Humans ; Infant ; Male ; Cell Cycle Proteins/genetics* ; Dyskeratosis Congenita/genetics* ; Exome Sequencing ; Fetal Growth Retardation/genetics* ; Intellectual Disability/genetics* ; Microcephaly/genetics* ; Mutation ; Nuclear Proteins/genetics* ; X-Linked Intellectual Disability/genetics*

Rett syndrome(RTT) is a severe and rare progressive developmental disorder, as a complex multisystem disease with a variety of clinical manifestations ranging from neurological to non-neurological symptoms.This article reviews the evidence-based update of RTT-related peripheral system comorbidities, so as to improve the understanding of RTT multisystem comorbidities and provide guidance for the multidisciplinary management of RTT patients.

Objective:To evaluate whether individualized dialectical treatment decoction taken for≥6 months after radical surgery for stageⅡ-Ⅲ colorectal cancer(CRC)is superior to surgery alone at preventing early(within 2 years)recurrence and metastasis.Methods:Patients with CRC who underwent radical surgery were enrolled consecutively in The First Affiliated Hospital of Henan University of CM and The First Affiliated Hospital of Henan University.The primary outcome was defined as early recurrence and metastasis for patients who underwent≥6 months of traditional Chinese medicine(TCM)treatment versus those who did not after surgery(Non-TCM).Multivariable modified Pois-son regression was used to model the primary outcome,and propensity score matching(PSM)was included in the regression-based sensit-ivity analysis.Results:A total of 103 patients received TCM treatment and 384 did not.In the entire cohort,the multivariable modified Pois-son regression model showed that the adjusted risk for early recurrence and metastasis was lower in the TCM group10.7%(12/103)vs.21.4%(82/384),relative risk(RR):0.448,95%confidence interval[CI]:0.261-0.769).PSM analysis was used at a 1:2 ratio,resulting in 99 pa-tients in the TCM group and 198 patients in the Non-TCM group.The TCM group still showed a lower risk for early recurrence and metastas-is 11.1%(11/99)vs.21.2%(42/198),RR:0.464,95%CI:0.227-0.948.The results of sensitivity analysis were consistent with multivariable ana-lysis.In this prespecified subgroup analysis,the difference in the rate of the primary outcome between the TCM and the Non-TCM groups was greater among males and those with N2 and moderately-highly differentiated tumors.Kaplan-Meier survival analysis showed that the incidence of early-recurrence-and metastasis-free survival was significantly higher in the TCM group than the Non-TCM groups.Conclusions:For patients with stage Ⅱ-Ⅲ colorectal cancer after radical surgery,individualized dialectical treatment with TCM was associated with a lower risk of early recurrence and metastasis.

Objective To investigate the risk factors related with the recurrence of multifocal papillary thyroid microcarcinoma(PTMC).Methods The data of 126 patients undergoing surgery from Jan.2001 to Jun.2011 proved to be multifocal PTMC by pathology were rctrospcctively analyzed.Logistic multifactor regression analysis was used to analyze the clinicopathological factors that may influence the recurrence of PTMC.Results The median age of the 126 patients was 46 years(ranging from 15 to 78 years old).The recurrence rate was 14.3％ (18/126) and the overall survival rate was 98.4％ with the medium follow-up of 75 months (ranging from 24 to 150 months).Multivariate analysis showed that extra-thyoidal extension,neck lymph node metastasis and non-total(or near total)thyroidectomy were the independent risk factors for the recurrence of multifocal PTMC (P =0.008,0.027,0.022 respectively).Conclusions Extension beyond the thyroid and metastatic neck lymph node predict a high risk of recurrence.Total or near total thyroidectomy can reduce the risk of recurrence.