A Rare Pathogenic Frameshift Mutation in NSD1 Gene Related to Sotos Syndrome in a Turkish Patient

Yıl 2021, Cilt: 35 Sayı: 2, 239 - 244, 30.08.2021

Pervin Elvan Tokgün

Öz

A Rare Pathogenic Frameshift Mutation in NSD1 Gene Related to Sotos Syndrome in a Turkish Patient

Öz

Sotos syndrome which autosomal dominant
inheritance has been observed, caused by the mutations
and deletions in NSD1 gene. NSD1 gene consists 23
exons and localizes on chromosome 5q35.3. The
prevalance of the Sotos syndrome is 1:14000 live births
and the disease is characterized by excessive growth
resulting in tall stature, a characteristical face
appearance, advanced bone age, neurological disorder
with intellectual disability and etc. Over 90% of the
patients represent overgrowth, learning disability and
macrocephaly. It has been shown that NSD1 gene
mutations and microdeletions in 5q35.3 were common
cause of Sotos syndrome. In this study we describe a 4
years old boy with Sotos syndrome harbouring a
pathogenic NSD1 frameshift mutation. Clinical exome
sequencing was performed using 2 ml of peripheral
blood sample of the patient. The high-throughput data
was analyzed using SOPHIA DDM database. The
pathogenity of the mutations were evaluated based on
in silico prediction tools (ClinVar, SIFT, Polyphen2,
MutationTaster).We detected a pathogenic frameshift
variant in NSD1 gene, 2386_2389delGAAA by clinical
exome sequencing. Although the diagnosis of Sotos
syndrome can be made clinically, molecular analyzes
are also important in diagnosis. Numerious NSD1 gene
mutations and deletions have been identified to date.
However, 2386_2389delGAAA pathogenic variant in
the NSD1 gene associated with Sotos syndrome will be
reported for the first time in Turkey.

Anahtar Kelimeler

Sotos syndrome, NSD1, clinical exome sequencing, Sotos syndrome, NSD1, clinical exome sequencing

Kaynakça

• Sohn YB, Lee CG, Ko JM, Yang JA, Yun JN, Jung EJ, et al. Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations. J Hum Genet. 2013; 58(2):73-7.
• 23. Cecconi M, Forzano F, Milani D, Cavani S, Baldo C, Selicorni A, et al. Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth. Am. J. Med. Genet. 2005; 134A: 247- 53.