Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations

Sohn, Young Bae; Lee, Cha Gon; Ko, Jung Min; Yang, Jung Ah; Yun, Jun No; Jung, Eun Jung; Jin, Hyun‐Seok; Park, Soo‐Jin; Jeong, Sun Young

doi:10.1038/jhg.2012.135

Cited by 14 publications

(8 citation statements)

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“…1). Recently, the first report of SS in Korea was published14), and this study documented that 53% of patients had a 5q35 microdeletion, a result that is very similar to that in Japan. Moreover, NSD1 abnormalities have been delineated in up to 90% of non-Japanese patients with Sotos syndrome, whereas approximately 30% of Japanese and Korean patients do not have NSD1 abnormalities14,15).…”

Section: Sotos Syndromesupporting

confidence: 63%

“…Recently, the first report of SS in Korea was published14), and this study documented that 53% of patients had a 5q35 microdeletion, a result that is very similar to that in Japan. Moreover, NSD1 abnormalities have been delineated in up to 90% of non-Japanese patients with Sotos syndrome, whereas approximately 30% of Japanese and Korean patients do not have NSD1 abnormalities14,15). 5q35 microdeletions can be detected by fluorescence in situ hybridization (FISH), multiplex ligation dependent probe amplification (MLPA), or array comparative genomic hybridization methods (array CGH), and NSD1 intragenic mutations can be identified by the direct sequencing method using the patient's genomic DNA.…”

Section: Sotos Syndromesupporting

confidence: 63%

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Genetic syndromes associated with overgrowth in childhood

2013

Ann Pediatr Endocrinol Metab

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Overgrowth syndromes comprise a diverse group of conditions with unique clinical, behavioral and molecular genetic features. While considerable overlap in presentation sometimes exists, advances in identification of the precise etiology of specific overgrowth disorders continue to improve clinicians' ability to make an accurate diagnosis. Among them, this paper introduces two classic genetic overgrowth syndromes: Sotos syndrome and Beckwith-Wiedemann syndrome. Historically, the diagnosis was based entirely on clinical findings. However, it is now understood that Sotos syndrome is caused by a variety of molecular genetic alterations resulting in haploinsufficiency of the NSD1 gene at chromosome 5q35 and that Beckwith-Wiedemann syndrome is caused by heterogeneous abnormalities in the imprinting of a number of growth regulatory genes within chromosome 11p15 in the majority of cases. Interestingly, the 11p15 imprinting region is also associated with Russell-Silver syndrome which is a typical growth retardation syndrome. Opposite epigenetic alterations in 11p15 result in opposite clinical features shown in Beckwith-Wiedemann syndrome and Russell-Silver syndrome. Although the exact functions of the causing genes have not yet been completely understood, these overgrowth syndromes can be good models to clarify the complex basis of human growth and help to develop better-directed therapies in the future.

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Section: Sotos Syndromesupporting

confidence: 63%

Section: Sotos Syndromesupporting

confidence: 63%

Genetic syndromes associated with overgrowth in childhood

2013

Ann Pediatr Endocrinol Metab

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“…In our case, the female patient had no family history, and the variant was de novo. This patient had typical facial abnormalities including reports (Grand et al, 2019;Sohn et al, 2013). In addition to the typical facial features of SS, she also showed hand deformities.…”

Section: Discussionmentioning

confidence: 80%

A novel nonsense variant in NSD1 gene in a female child with Sotos syndrome: A case report and literature review

Liu,

Chen,

Wan

et al. 2023

Brain and Behavior

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IntroductionSotos syndrome (SS) is an overgrowth disease characterized by distinctive facial features, advanced bone age, macrocephaly, and developmental delay is associated with alterations in the NSD1 gene. Here, we report a case of a 4‐year‐old female child with SS caused by NSD1 gene nonsense mutation.MethodsWhole‐exome sequencing (WES) was applied for probands and her parents. Sanger sequencing was used to confirm the mutation. We performed the literature review using PubMed and found 12 articles and 14 patients who presented with SS.ResultsThe patient showed typical facial features of SS, hand deformities, and seizure. WES revealed de novo heterozygous variant: NSD1 (NM_022455.5), c.6095G > A, p.TRP2032*. We also reviewed the phenotype spectrum of 14 patients with SS, who exhibited a variety of clinical phenotypes, including developmental delay, seizures, scoliosis, hearing loss, cardiac and urinary system abnormalities, and so on.DiscussionThe lack of correlation between mutation sites or types and phenotypes was summarized by literature reviewing. The NSD1 protein contains 14 functional domains and this nonsense mutation was located in SET domain. Early appearance of the termination codon leads to protein truncation. Haploinsufficiency of the NSD1 gene causes the overgrowth disorders.

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“…Altogether, these genomic alterations reach to a significant number [ 26 – 28 ]. Compared to deletions [ 27 , 29 – 33 ] duplications in the region are rare and not well-characterized [ 34 – 37 ]. Moreover, there is no well-established genotype-phenotype correlation for these gains currently since they are in variable sizes and lack precise breakpoints.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel genomic imbalances in Saudi patients with congenital heart disease

et al. 2018

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BackgroundQuick genetic diagnosis of a patient with congenital heart disease (CHD) is quite important for proper health care and management. Copy number variations (CNV), chromosomal imbalances and rearrangements have been frequently associated with CHD. Previously, due to limitations of microscope based standard karyotyping techniques copious CNVs and submicroscopic imbalances could not be detected in numerous CHD patients. The aim of our study is to identify cytogenetic abnormalities among the selected CHD cases (n = 17) of the cohort using high density oligo arrays.ResultsOur screening study indicated that six patients (~35%) have various cytogenetic abnormalities. Among the patients, only patient 2 had a duplication whereas the rest carried various deletions. The patients 1, 4 and 6 have only single large deletions throughout their genome; a 3.2 Mb deletion on chromosome 7, a 3.35 Mb deletion on chromosome 3, and a 2.78 Mb a deletion on chromosome 2, respectively. Patients 3 and 5 have two deletions on different chromosomes. Patient 3 has deletions on chromosome 2 (2q24.1; 249 kb) and 16 (16q22.2; 1.8 Mb). Patient 4 has a 3.35 Mb an interstitial deletion on chromosome 3 (3q13.2q13.31).Based on our search on the latest available literature, our study is the first inclusive array CGH evaluation on Saudi cohort of CHD patients.ConclusionsThis study emphasizes the importance of the arrays in genetic diagnosis of CHD. Based on our results the high resolution arrays should be utilized as first-tier diagnostic tool in clinical care as suggested before by others. Moreover, previously evaluated negative CHD cases (based on standard karyotyping methods) should be re-examined by microarray based cytogenetic methods.

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Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations

Cited by 14 publications

References 25 publications

Genetic syndromes associated with overgrowth in childhood

Genetic syndromes associated with overgrowth in childhood

A novel nonsense variant in NSD1 gene in a female child with Sotos syndrome: A case report and literature review

Identification of novel genomic imbalances in Saudi patients with congenital heart disease

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