Analysis of the NSD1 promoter region in patients with a Sotos syndrome phenotype

Visser, Remco; Hasegawa, Tomonobu; Niikawa, Norio; Matsumoto, Naomichi

doi:10.1007/s10038-005-0314-0

Cited by 3 publications

(4 citation statements)

References 29 publications

(38 reference statements)

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“…Truncating NSD1 mutations occured throughout the gene, but pathogenic missense mutations occurred only in functional domains [ 10 , 45 ]. To date, no hypermethylation or sequence abnormalities in the promotor region have been detected in Sotos patients [ 46 ].…”

Section: Etiologymentioning

confidence: 99%

Sotos syndrome

Baujat¹,

Cormier‐Daire²

2007

Orphanet J Rare Dis

123

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Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC), advanced bone age, neonatal complications including hypotonia and feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes. Variable delays in cognitive and motor development are also observed. The syndrome may also be associated with an increased risk of tumors. Mutations and deletions of the NSD1 gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated in transcriptional regulation) are responsible for more than 75% of cases. FISH analysis, MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and direct sequencing allows detection of NSD1 mutations. The large majority of NSD1 abnormalities occur de novo and there are very few familial cases. Although most cases are sporadic, several reports of autosomal dominant inheritance have been described.

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Section: Etiologymentioning

confidence: 99%

Sotos syndrome

Baujat¹,

Cormier‐Daire²

2007

Orphanet J Rare Dis

123

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“…[1415] Weaver's syndrome is similar and closely related to Sotos syndrome, with advanced carpal maturation, widened distal long bones and campodactyly. NSD1 intragenic mutation is also noted in Weaver's patients.…”

Section: Discussionmentioning

confidence: 99%

Sotos syndrome: An interesting disorder with gigantism

Nalini

Biswas

2008

Ann Indian Acad Neurol

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We report the case of a 16-year-old boy diagnosed to have Sotos syndrome, with rare association of bilateral primary optic atrophy and epilepsy. He presented with accelerated linear growth, facial gestalt, distinctive facial features, seizures and progressive diminution of vision in both eyes. He had features of gigantism from early childhood. An MRI showed that brain and endocrine functions were normal. This case is of interest, as we have to be aware of this not so rare disorder. In addition to the classic features, there were two unusual associations with Sotos syndrome in the patient.

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“…The phenotype of Sotos syndrome has been shown to be mostly independent of the underlying NSD1 defect, although cases with 5q35 microdeletions have been reported to suffer a higher degree of learning disability and less pronounced overgrowth. 1,[3][4][5][6] The association between the clinical features seen in Sotos syndrome patients (i.e., cardiac abnormalities, renal abnormalities, seizures, and scoliosis) and the various types of NSD1 gene aberrations such as the 5q35 microdeletion and various intragenic pathogenic variants (i.e., missense, nonsense, frameshift, and truncation mutations) have been investigated, 2,7-10 but no apparent genotype-phenotype correlation has been uncovered. 11 Although scoliosis has been reported in approximately 30% of Sotos syndrome patients, 1 the genetic background of this associated symptom has not been sufficiently studied.…”

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confidence: 99%

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The Association of Scoliosis and NSD1 Gene Deletion in Sotos Syndrome Patients

Machida

Katoh

Machida

et al. 2020

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Study Design. A retrospective comparative study.Objective. The aim of this study was to examine the NSD1 abnormalities in patients diagnosed with Sotos syndrome and its correlation with the presence, severity, and progression of associated scoliosis. Summary of Background Data. Scoliosis has been reported in approximately 30% of patients diagnosed with Sotos syndrome, a genetic disorder characterized by a distinctive facial appearance, learning disability, and overgrowth. Sotos syndrome is mainly attributed to NSD1 haploinsufficiency, but with ethnical differences in genetic profile: NSD1 microdeletions are frequently identified in Japanese Sotos patients whereas intragenic mutations are more frequently found in non-Japanese patients. Although possible genotype-phenotype correlations have been proposed, the genotype of Sotos syndrome patients suffering from scoliosis has not been examined. Methods. The medical records and spinal radiographs of 63 consecutive Sotos syndrome patients at a single center were reviewed. Fluorescent in situ hybridization or microarray comparative genomic hybridization and DNA sequencing or multiplex ligation-dependent probe amplification were performed to detect 5q35 microdeletion involving the NSD1 gene and intragenic mutations of the NSD1 gene, respectively. The phenotypes of all cases and radiological assessments for the presence and progression of scoliosis were studied. Results. NSD1 abnormalities were identified in 55 patients (87%): microdeletion in 34 patients (54%) and intragenic mutation in 22 patients (33%). Scoliosis was observed in 26 patients (41%), with a significantly higher ratio of microdeletions than mutations. The 10 patients with progressive scoliosis all had NSD1 microdeletions. Conclusion. Scoliosis was a common phenotypical trait in children with Sotos syndrome and its presence as well as progression were higher in cases with NSD1 microdeletions. Although all Sotos syndrome patients should be monitored for scoliosis, clinicians should be made aware that patients with NSD1 microdeletions have a higher probability of scoliosis development and progression that may require early intervention.

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Analysis of the NSD1 promoter region in patients with a Sotos syndrome phenotype

Cited by 3 publications

References 29 publications

Sotos syndrome

Sotos syndrome

Sotos syndrome: An interesting disorder with gigantism

The Association of Scoliosis and NSD1 Gene Deletion in Sotos Syndrome Patients

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