Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome

Lin, Yunting; Chen, Xiaohong; Xie, Bobo; Guan, Zhihong; Chen, Xiaodan; Li, Xiuzhen; Yi, Peng; Du, Rong; Mei, Hongbing; Liu, Li; Zhang, Wen; Zeng, Chunhua

doi:10.3389/fgene.2023.1085210

Cited by 3 publications

(1 citation statement)

References 38 publications

(77 reference statements)

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“…Genomic DNA (gDNA) was extracted from peripheral blood samples using DNeasy Blood and Tissue Kit (QIAGEN, Hilden, Germany). WES was performed as previously described [ 13 , 14 ]. To validate the COL2A1 variant identified by WES, the classic Sanger sequencing of the PCR products targeting the exon 42 of the COL2A1 gene (NG_008072.1, NM_001844.5) was carried out.…”

Section: Methodsmentioning

confidence: 99%

Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family

Zhang

Ding

et al. 2023

Calcif Tissue Int

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Rare genetic skeletal disorders (GSDs) remain the major problem in orthopedics and result in significant morbidity in patients, but the causes are highly diverse. Precise molecular diagnosis will benefit management and genetic counseling. This study aims to share the diagnostic experience on a three-generation Chinese family with co-occurrence of spondyloepiphyseal dysplasia (SED) and X-linked hypophosphatemia (XLH), and evaluate the therapeutic effects of two third-generation siblings. The proband, his younger brother, and mother presented with short stature, skeletal problems, and hypophosphatemia. His father, paternal grandfather, and aunt also manifested short stature and skeletal deformities. Whole exome sequencing (WES) of proband–brother–parents initially only found the proband and his younger brother had a pathogenic c.2833G > A(p.G945S) variant in the COL2A1 gene inherited from their father. Re-analysis of WES uncovered the proband and his younger brother also harbored a pathogenic ex.12 del variant in the PHEX gene transmitted from their mother. Sanger sequencing, agarose gel electrophoresis, and quantitative polymerase chain reaction proved these results. The proband and his younger brother were confirmed to have a paternally inherited SED and a maternally inherited XLH. During a 2.8-year follow-up, these two siblings remained short stature and hypophosphatemia, but their radiographic signs and serum bone alkaline phosphatase levels were improved with treatment of oral phosphate and calcitriol. Our study presents the first report of co-occurrence of SED and XLH, shows the possibility that two different rare GSDs co-exist in a single patient, and alerts clinicians and geneticists to be cautious about this condition. Our study also suggests that next-generation sequencing has limit in detecting exon-level large deletions.

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Section: Methodsmentioning

confidence: 99%

Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family

Zhang

Ding

et al. 2023

Calcif Tissue Int

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Determining the Linguistic Profile of Children With Rare Genetic Disorders

Espinosa-Mojica,

Varo Varo

2024

J Speech Lang Hear Res

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Purpose: Language studies on populations with rare genetic disorders are limited. Hence, there is little data on commonly found or expected developmental linguistic traits and cognitive mechanisms that may be impaired. Based on the hypothesis that there is a close connection between language and cognition and the relevance of specific genetic changes in the development of each, our goal was to provide linguistic data on relationships with other executive functioning mechanisms. Method: This study assessed language skills, communicative behaviors, and executive functions in four children, aged 7–9 years, with rare genetic disorders, using standardized protocols and tests. Results: The findings revealed different levels of language impairment and executive functioning problems in each case. The overall executive function index performance for each of the four cases studied was clinically significantly high, indicating executive dysfunction. Conclusions: The cases analyzed illustrate different types of atypical development that affect both language and other cognitive mechanisms and underscore the importance of executive skills and the various ways in which they are involved in diverse levels of language that might be affected to a greater or lesser degree in rare genetic disorders. In conclusion, we found that language dysfunction is a salient feature of the rare genetic disorders included in our study, although this is not necessarily true for all genetic disorders. Along with these conclusive results, we performed a qualitative analysis of the linguistic and cognitive components that enable functional communication in order to allow optimal interpretation of the data we have collected, laying the foundations for a more effective therapeutic approach.

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Two Chinese Patients of Auriculocondylar Syndrome 2: A Novel PLCB4 Splicing Variant and 5-Year Follow-up

Lin,

Zhang,

et al. 2024

The Cleft Palate Craniofacial Journal

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Objective Auriculocondylar syndrome (ARCND) is a set of rare craniofacial malformations characterized by variable micrognathia, ear malformations, and mandibular condyle hypoplasia, and other accompanying features with phenotypic complexity. ARCND2 caused by pathogenic variants in the PLCB4 gene is a very rare disease with less than 50 patients reported and only 36 different variants of the PLCB4 gene recorded in HGMD. This study aims to enrich the patient resources, clinical data and mutational spectrum of ARCND2. Design Case series study. Setting Guangzhou Women and Children's Medical Center and Guangdong Women and Children Hospital. Patients Two Chinese patients with ARCND2. Main Outcome Measures Clinical, radiological and molecular findings. Results Both the two patients presented with craniofacial and ear malformations, and feeding difficulties. Whole exome sequencing identified two different variants of the PLCB4 gene in these two patients with a heterozygous allele and a de novo mode of inheritance respectively. Patient 1 carried a known pathogenic c.1861C > T(p.Arg621Cys) missense variant, whereas Patient 2 had a novel c.225 + 1G > A splicing variant. Sanger sequencing confirmed the presence of PLCB4 variants in the proband and absence in the unaffected parents. These two PLCB4 variants were suggested as disease-causing candidates for these two patients. During a 5-year follow-up, Patient 2 gradually manifested crowded teeth, underweight, motor delay and intellectual disability. Conclusions In this study, we report two Chinese patients with ARCND2, describe their clinical and mutational features, and share a 5-year follow-up of one patient. Our study adds two additional patients to ARCND2, reveals a novel PLCB4 variant, and expands the phenotypic and genotypic spectrum.

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Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome

Cited by 3 publications

References 38 publications

Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family

Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family

Determining the Linguistic Profile of Children With Rare Genetic Disorders

Two Chinese Patients of Auriculocondylar Syndrome 2: A Novel PLCB4 Splicing Variant and 5-Year Follow-up

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