Dataset Information

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

ABSTRACT:

Introduction

Sotos 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.

Methods

Whole-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.

Results

The 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.

Discussion

The 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.

SUBMITTER: Liu X

PROVIDER: S-EPMC10726859 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Liu Xinting X Chen Chen C Wan Lin L Zhu Gang G Zhao Yan Y Hu Lizhu L Liang Yan Y Gao Jing J Wang Jing J Yang Guang G

Brain and behavior 20231031 12

<h4>Introduction</h4>Sotos 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.<h4>Methods</h4>Whole-exome sequencing (WES) was applied for probands and her parents. Sanger sequencing was used to confirm the mutation. We performed the literature review using PubM ...[more]

PMID: 37908045

Similar Datasets

Project description:Sotos syndrome (SoS) is characterized by overgrowth of prenatal onset, learning disability, and characteristic facial appearance; it is usually due to haploinsufficiency of NSD1 gene at chromosome 5q35. An Italian child was born at 37 weeks of gestation (weight 2,910 g, 25th-50th centiles; length 50 cm, 75th centile; head circumference 36 cm, 97th centile) showing cryptorchidism on the right side, hypertelorism, dolichocephaly, broad and prominent forehead, and narrow jaw; the pregnancy was worsened by maternal preeclampsia and gestational diabetes, and his mother had a previous history of four early miscarriages. The patient showed neonatal jaundice, hypotonia, feeding difficulties, frequent vomiting, and gastroesophageal reflux. After the age of 6 months, his weight, length, and head circumference were above the 97th centile; psychomotor development was delayed. At the age of 9 years, the patient showed also joint laxity and scoliosis. DNA sequence analysis of NSD1 gene detected a novel heterozygous mutation (c.521T>A, p.Val174Asp) in exon 2. The same mutant allele was also found in the mother and in the maternal grandfather of the proband; both the mother and the maternal grandfather of the proband showed isolated overgrowth with height above the 97th centile in absence of other features of SoS. At present 23 familial cases of SoS have been described (two cases with mutation in exon 2 of NSD1 gene); no familial cases of SoS with mutation of NSD1 gene and isolated overgrowth have been reported. Probably, point mutations of NSD1 gene, and particularly mutations between exon 20 and exon 23, are not likely to affect reproductive fitness. Epigenetic mechanisms and intrauterine environment may influence phenotypes, therefore genetic tests are not useful to predict the phenotype but they are indispensable for the diagnosis of SoS. This is the first Italian familial case of SoS with genetic confirmation and the third report in which a missense mutation of NSD1 gene is found in three generations of the same family.

Dataset Information

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

Introduction

Methods

Results

Discussion

Publications

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

Similar Datasets

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