Sotos, Sotos-like, Marshall-Smith, Luscan-Lumish syndroom, Tatton-Brown-Rahman, Weaver syndrome

OMIM :

Sotos syndrome 1                                : 117550

Sotos-like syndrome (Sotos syndrome 2): 614753

Marshall-Smith syndrome                     : 602535

Luscan-Lumish syndrome                     : 616831

Tatton-Brown-Rahman syndrome          : 615879

Rahman syndrome                               : 617537

Weaver syndrome                                 : 277590

 

Gene

Techniques

NSD1

  • Sequence analysis of the entire coding region (exons 2 to 23) including intron/exon boundaries. 
  • MLPA of exons 1 to 23 (MRC-Holland kit P026-E1) for the detection of deletions and duplications.

NFIX

  • Sequence analysis of the entire coding region  (exons 2 - 11) including intron/exon junctions
  • MLPA exons 2 t/m 11 (P026-E1) for the detection of deletions and duplications

SETD2

  • Sequence analysis of the entire coding region  (exon 1 - 21) including intron/exon junctions

DNMT3A

  • Sequence analysis of the entire coding region  (exon 2 - 23) including intron/exon junctions

HIST1H1E

  • Sequence analysis exon 1 including intron/exon junctions

EZH2

  • Sequence analysis of the entire coding region (exons 2 to 20), including intron/exon boundaries

Procedure :

Sotos syndrome diagnostic includes both sequencing and MLPA as standard. If no mutation is found, testing of NFIX, SETD2, DNMT3A and HIST1H1E (Sotos-like syndrome) and EZH2 (Weaver syndrome) are also possible.

For Sotos-like and Marshall-Smith syndrome the same procedure is performed; i.e. sequence analysis and MLPA of NIFIX. In addition, sequence analysis of SETD2 (Luscan-Lumish syndrome), DNMT3A (Tatton-Brown-Rahman syndroem) and HIST1H1E ( Rahman syndrome) is performed.

MLPA is not performed for EZH2 (Weaver syndrome) because only missense and truncating mutations in the last exon have been described in patients with this syndrome (see Tatton-Brown and Rahman, 2013).

Detection ratio:  

Sotos syndrome 1: Approximately 33%; higher in cases with strong clinical suspicion

Sotos-like syndrome: not known, but appears very rare (See also Malan et al., 2010)

Marshall-Smith syndrome: high (See also Malan et al., 2010)

Weaver syndrome: Not yet known

 

Gene

Gene product

Locus

Inheritance

OMIM number

Reference Sequence

NSD1

Nuclear receptor binding SET domain protein

5q35.2-q35.3

Autosomal dominant, de novo

606681

NC_000005.8, NM_022455.4

NFIX

Nuclear factor I/X

19p13.2

Autosomal dominant, de novo (both syndromes)

164005

NC_000019.9, ENST00000592199.1 (this transcript includes also NM_002501.2).

SETD2

SET domain-containing protein 2

3p21.31

Autosomal dominant, de novo

612778

NC_000003.12, NM_014159.6

DNMT3A

DNA methyltransferase

2p23.3

Autosomal dominant, de novo

602769

NC_000002.12, NM_022552.4

HIST1H1E

Histone gene cluster 1, h1 histone family, member e

6p22.2  

Autosomal dominant

142220

NC_000006.11, NM_005321.2

EZH2

Enhancer of Zeste Homolog 2

7q36.1

Autosomal dominant, de novo

601573

NG_032043.1, NM_004456.4

Website links:

Sending patient material

Laboratory turnaround times

 

Databases / links:

 

  • Malan, V. et al. Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall-Smith syndrome. Am J Hum Genet. 201013;87(2):189-98.

·          Tatton-Brown K, Rahman N. The NSD1 and EZH2 overgrowth genes, similarities and differences. Am J Med Genet C Semin Med Genet. 2013;163C(2):86-91.