Chromosome 5q14.3 Deletion Syndrome via the MEF2C Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4187 MEF2C 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4187MEF2C81479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Chromosome 5q14.3 deletion syndrome (OMIM:613443) is a neurocognitive disorder characterized by epilepsy and intellectual disability. 5q14.3 deletion syndrome patients show signs of psychomotor delay at around 6 months and many never develop speech. Onset of tonic-clonic seizures occurs during infancy and early childhood. Seizures are usually well controlled with medication (Zweier and Rauch 2011). Other symptoms include muscular hypotonia and limited ability to walk. Brain MRI can reveal various anomalies such as delayed myelination, thickened corpus callosum or enlarged ventricles, but there is no common finding among patients. 5q14.3 deletion syndrome patients share a similar facial gestalt including a broad forehead, flat nose, Cupid's bow lip, macrodontia and strabismus (Zweier et al. 2010). Other rare features seen in a subset of patients include stereotyped hand movements, poor eye contact and autistic features.

Genetics

5q14.3 deletion syndrome is most commonly caused by large deletions encompassing the MEF2C gene. Most identified 5q14.3 deletions include the MEF2C gene as well as neighboring genes, but deletions limited to the MEF2C gene have been identified (Nowakowska et al. 2010; Le Meur et al. 2010). De novo nonsense and missense mutations in the MEF2C gene also result in a phenotype that resembles 5q14.3 deletion syndrome, suggesting that MEF2C haploinsufficiency underlies the disorder (Zweier et al. 2010; Le Meur et al. 2010). A handful of 5q14.3 duplications including the MEF2C gene have been reported and patients present with mild intellectual disability, microcephaly and impaired speech (Novara et al. 2013).

MEF2C encodes a transcription factor that is highly expressed in the muscle, heart and brain. Knocking out MEF2C expression in the mouse brain results in reduced neuronal differentiation and neural networks with fewer synapses and impaired electrical activity. MEF2C knockout mice also had anxious behavior, decreased cognitive function and stereotyped paw motions thus mimicking some features of 5q14.3 deletion syndrome (Li et al. 2008).

Clinical Sensitivity - Sequencing with CNV PG-Select

One study identified de novo mutations in the MEF2C gene in ~1.8% (4 of 221) of patients with severe intellectual disability but without gross malformations or specific dysmorphisms (Zweier et al. 2010).

Testing Strategy

This test provides full coverage of all coding exons of the MEF2C gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

MEF2C testing is recommended in patients with symptoms of 5q14.3 deletion syndrome, particularly childhood-onset epilepsy with intellectual disability and hypotonia.

Gene

Official Gene Symbol OMIM ID
MEF2C 600662
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Li H, Radford JC, Ragusa MJ, Shea KL, McKercher SR, Zaremba JD, Soussou W, Nie Z, Kang Y-J, Nakanishi N. 2008. Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo. Proceedings of the National Academy of Sciences 105: 9397–9402. PubMed ID: 18599437
  • Meur N Le, Holder-Espinasse M, Jaillard S, Goldenberg A, Joriot S, Amati-Bonneau P, Guichet A, Barth M, Charollais A, Journel H, Auvin S, Boucher C, et al. 2010. MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations. J. Med. Genet. 47: 22–29. PubMed ID: 19592390
  • Novara F, Rizzo A, Bedini G, Girgenti V, Esposito S, Pantaleoni C, Ciccone R, Sciacca FL, Achille V, Della Mina E, Gana S, Zuffardi O, et al. 2013. MEF2C deletions and mutations versus duplications: A clinical comparison. European Journal of Medical Genetics 56: 260–265. PubMed ID: 23402836
  • Nowakowska BA, Obersztyn E, Szymańska K, Bekiesińska-Figatowska M, Xia Z, Ricks CB, Bocian E, Stockton DW, Szczałuba K, Nawara M, Patel A, Scott DA, et al. 2010. Severe mental retardation, seizures, and hypotonia due to deletions of MEF2C. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 153B(5):1042-1051. PubMed ID: 20333642
  • Zweier M, Gregor A, Zweier C, Engels H, Sticht H, Wohlleber E, Bijlsma EK, Holder SE, Zenker M, Rossier E, Grasshoff U, Johnson DS, et al. 2010. Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression. Human Mutation 31: 722–733. PubMed ID: 20513142
  • Zweier M, Rauch A. 2011. The MEF2C -Related and 5q14.3q15 Microdeletion Syndrome. Molecular Syndromology 2: 164–170. PubMed ID: 22670137

Ordering/Specimens

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