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. 2022 Sep;10(9):e2009.
doi: 10.1002/mgg3.2009. Epub 2022 Jul 10.

Ten-year follow-up of Nicolaides-Baraitser syndrome with a de novo mutation and analysis of 58 gene loci of SMARCA2-associated NCBRS

Xilian Zhang  1   2 , Hanjiang Chen  1   2 , Ying Song  3 , Zhaoyuan Chen  3 , Xuan Liu  1   2 , Ping Rong  1   2 , Rong Ma  1   2
Affiliations

Ten-year follow-up of Nicolaides-Baraitser syndrome with a de novo mutation and analysis of 58 gene loci of SMARCA2-associated NCBRS

Xilian Zhang et al. Mol Genet Genomic Med. 2022 Sep.

Abstract

As a clinical subtype of SWI/SNF-related intellectual disability syndromes, Nicolaides-Baraitser syndrome (NCBRS, OMIM601358) has a unique genotype-phenotype. Due to the scarcity of the number of cases reported and the limitations of diagnosis methods, so far only more than 80 cases have been reported worldwide. In this article, a new patient with a de novo mutation was followed up for 10 years; it includes the epilepsy treatment process, the characteristics of NBCRS with seizures, typical faces, sparse hair, prominent interphalangeal joints, and intellectual disability, and we also summarized the genotype-phenotype of the 80 reported cases for comparison. Due to insufficient studies and lack of attention paid to the syndrome, it is believed that the actual number of cases should be far more than the reported number. The syndrome is phased and progressive. The genotype-phenotype correlation of the disease is related to the location of the gene locus, especially closely related to the SNF2 ATPase domain. CONCLUSIONS: The understanding of NCBRS is lagging, we need to strengthen the screening process of the phenotypic disease with intellectual disability, and perfecting multiple types of diagnostic techniques will help the discovery of the disease; its clinical features are staged and are slowly progressive, and long-term prognosis must be taken precautious with long-term follow-up required.

Keywords: Nicolaides-Baraitser syndrome; SMARCA2; evolving features; genotype.

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Conflict of interest statement

The authors declare no potential conflicts of interest in relation to this article.

Figures

FIGURE 1
FIGURE 1
The changes in facial morphology and distal limbs in 10 years. (a) 1 year, (b) 2 years, (c) 4 years, (d) 5 years, (e) 6 years, (f) 7 years, (g) 8 years, (h) 10 years. These photos showed this child with a narrow forehead, low anterior hairline, wide nasal bridge, broad nasal base, broad and long philtrum, large mouth and thin upper vermillion at different periods, and facial skin began to be rough, ptosis, increased skin wrinkling with aged. Foot and hand images (i–l) showed that prominent interphalangeal joints and distal phalangeal, foot sandal gap, and nail anomalies.
FIGURE 2
FIGURE 2
The three‐dimensional structure diagram of NM_003070.4:c.3313C>T. (KingMed Diagnostic, NP18D932) showed that the mutation was located at Exon24, c.3313C>T, p. (Arg1105Cys). His parents' genetic analysis did not detect pathogenic genes. The 3D protein structure was predicted by the Swiss‐Prot web tool to check the effect of amino acid change in position 1105 resultant from the variation of c.3314G>A. The 15–25 exons region is the SNF2 ATPase domain, it contains the N‐terminal domain and C‐terminal domain. The 508–1305 amino acids (structure in the figure) of SMARCA2 have 58.25% similarity with SNF2‐family ATP‐dependent chromatin remodeling factor‐like protein; the 1105th amino acid is located in the α‐helix structure of the helicase C‐terminal domain. The start and end amino acids of the α‐helix are 1102–1113. No matter whether the 1105th amino acid is Arg or Cys, it does not change the shape of the helix structure.
FIGURE 3
FIGURE 3
The distribution of 58 de novo mutation sites. Among the 58 de novo sites related to NCBRS, 52 sites are missense mutation, the other sites are in‐frame deletion (two cases), frameshift mutation (two cases), intron mutation (one case), and nonsense mutation (one case), respectively. Most of de novo sites are located at the SNF2 ATPase domain, which is directly related to phenotypes.
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