Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome

Luo, Sukun; Bi, Bo; Zhang, Wenqian; Zhou, Rui; Chen, Wei; Zhao, Peiwei; Huang, Yufeng; Li, Yuan; He, Xuelian

doi:10.1002/mgg3.1798

Cited by 5 publications

(4 citation statements)

References 27 publications

(47 reference statements)

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“…In addition, to fully investigate the phenotypic spectrum of Chinese WSS patients, 41 of 43 previously reported Chinese WSS patients with available identify information were reviewed and included in our analysis [( Sun et al, 2017 ; Gao et al, 2018 ; Li et al, 2018 ; Chen et al, 2019 ; Dai et al, 2019 ; Shangguan et al, 2019 ; Jinxiu et al, 2020 ; Wang et al, 2021a ; Wang et al, 2021b ; Feng et al, 2021 ; Lee et al, 2021 ; Luo et al, 2021 ; Sheppard et al, 2021 ; Xue et al, 2021 ; Chen et al, 2022 ; Wu et al, 2022 ; Yu et al, 2022 ), and other 4 literatures in Chinese], which increases the total sample size to 52.…”

Section: Resultsmentioning

confidence: 99%

“…WSS is a rare disease and far away from well-known in China. To best of our knowledge, 43 Chinese WSS patients have been reported [( Sun et al, 2017 ; Gao et al, 2018 ; Li et al, 2018 ; Chen et al, 2019 ; Dai et al, 2019 ; Shangguan et al, 2019 ; Jinxiu et al, 2020 ; Wang et al, 2021a ; Wang et al, 2021b ; Feng et al, 2021 ; Lee et al, 2021 ; Luo et al, 2021 ; Sheppard et al, 2021 ; Xue et al, 2021 ; Chen et al, 2022 ; Wu et al, 2022 ; Yu et al, 2022 ), and other 4 literatures in Chinese]. Among them, only one was Chinese cohort study ( Li et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Due to highly clinical heterogeneity and phenotypic similarity with other disorders, WSS is far away from well-known. The prevalence of WSS is estimated to be less than 1/1,000,000 ( Luo et al, 2021 ). To date, less than 400 WSS patients have been reported in the worldwide, and some affected adults are not yet recognized until their child’s diagnosis ( Sheppard et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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Objective: Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant disorder caused by deleterious heterozygous variants of the KMT2A gene. This study aims to describe the phenotypic and genotypic features of Chinese WSS patients, and assess therapeutic effects of recombinant human growth hormone (rhGH).Methods: Eleven Chinese children with WSS were enrolled in our cohort. Their clinical, imaging, biochemical and molecular findings were analyzed retrospectively. Moreover, the phenotypic features of 41 previously reported Chinese WSS patients were reviewed and included in our analysis.Results: In our cohort, the 11 WSS patients presented with classic clinical manifestations, but with different frequencies. The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%). The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain. In the set comprising 52 Chinese WSS patients, the most common clinical and imaging manifestations were developmental delay (84.6%), intellectual disability (84.6%), short stature (80.8%) and delayed bone age (68.0%), respectively. Eleven different variants, including three known and eight novel variants, of the KMT2A gene were identified in our 11 WSS patients without a hotspot variant. Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age.Conclusion: Our study adds 11 new patients with WSS, reveals different clinical characteristics in Chinese WSS patients, and extends the mutational spectrum of the KMT2A gene. Our study also shares the therapeutic effects of rhGH in two WSS patients without GH deficiency.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…It has two AT-hook DNA binding domains (347-359 and 381-393), which may be involved in regulating DNA-dependent processes. Genes with an AT-hook DNA binding domain, such as MECP2, are involved in human neurodevelopmental disorders (14)(15)(16). Furthermore, PRR12 has an identified epigenetic modification site, lysine acetylation site (N6-acetyllysine), suggest its potential involvement in epigenetic regulation (13).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Identification of a novel PRR12 variant in a Chinese boy with developmental delay and short stature

Liu,

Ding,

et al. 2024

Front. Pediatr.

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Proline Rich 12 (PRR12) protein is primarily expressed in the brain and localized in the nucleus. The variants in the PRR12 gene were reported to be related to neuroocular syndrome. Patients with PRR12 gene presented with intellectual disability (ID), neuropsychiatric disorders, some congenital anomalies, and with or without eye abnormalities. Here, we report an 11-year-old boy with a novel PRR12 variant c.1549_1568del, p.(Pro517Alafs*35). He was the first PRR12 deficiency patient in China and presented with ID, short stature, and mild scoliosis. He could not concentrate on his studies and was diagnosed with attention deficit hyperactivity disorder (ADHD). The insulin-like growth factor 1 (IGH-1) was low in our patient, which may be the cause of his short stature. Patients with neuroocular syndrome are rare, and further exploration is needed to understand the reason for neurodevelopmental abnormalities caused by PRR12 variants. Our study further expands on the PRR12 variants and presents a new case involving PPR12 variants.

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Epigenetic regulation of craniofacial development and disease

Shull,

Artinger

2023

Birth Defects Research

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BackgroundThe formation of the craniofacial complex relies on proper neural crest development. The gene regulatory networks (GRNs) and signaling pathways orchestrating this process have been extensively studied. These GRNs and signaling cascades are tightly regulated as alterations to any stage of neural crest development can lead to common congenital birth defects, including multiple syndromes affecting facial morphology as well as nonsyndromic facial defects, such as cleft lip with or without cleft palate. Epigenetic factors add a hierarchy to the regulation of transcriptional networks and influence the spatiotemporal activation or repression of specific gene regulatory cascades; however less is known about their exact mechanisms in controlling precise gene regulation.AimsIn this review, we discuss the role of epigenetic factors during neural crest development, specifically during craniofacial development and how compromised activities of these regulators contribute to congenital defects that affect the craniofacial complex.

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Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 5 publications

References 27 publications

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

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

Case Report: Identification of a novel PRR12 variant in a Chinese boy with developmental delay and short stature

Epigenetic regulation of craniofacial development and disease

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