2q23.1 Microdeletion Syndrome and Autism Spectrum Disorder via the MBD5 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
4183 MBD5 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4183MBD581479 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

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Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Autosomal dominant intellectual disability via 2q23.1 microdeletion syndrome is a neurocognitive disorder characterized by moderate to severe intellectual disability and motor delay. 2q23.1 microdeletion syndrome patients often present in infancy with hypotonia and feeding difficulties. During childhood patients may develop seizures, stereotypic hand movements, sleep disturbances, short attention span and autistic-like behaviors (Talkowski et al. 2011). 2q23.1 microdeletion syndrome patients exhibit severe language impairment, often not being able to speak meaningful words. Physical features of patients with 2q23.1 microdeletion syndrome include thick arched eyebrows, broad forehead, downturned mouth and thin upper lip (Hodge et al. 2013).

Gross deletions of the 2q23.1 region results in a more severe clinical phenotype than variations that affect only the MBD5 gene, suggesting other genes in the deletion interval contribute to the phenotype. Additional features seen in large 2q23.1 deletion cases include an ataxic gait, self-injurious behaviors, hyperphagia and obesity, pinnae abnormalities, microcephaly and short fifth digit of hands and feet (Talkowski et al. 2011).

2q23.1 microduplications have also been reported in patients with intellectual disability. The most common features of 2q23.1 microduplication syndrome are psychomotor delay, language impairment, infantile hypotonia, behavioral problems and autistic-like symptoms (Mullegama et al. 2013). Shared facial features observed in patients include downslanting palpebral fissures, arched eyebrows, long eyelashes, prominent nose and pinnae abnormalities.

Genetics

2q23.1 microdeletion syndrome is caused by deletions encompassing the MBD5 gene. 2q23.1 microdeletion syndrome is an autosomal dominant disorder and many cases are sporadic, resulting from de novo deletions encompassing the MBD5 gene. Causative nonsense and frameshift mutations in MBD5 have also been reported in patients with intellectual disability (Kleefstra et al. 2012; Bonnet et al. 2013). A number of missense variants in MBD5 have been reported in patients with intellectual disability or autism, but the causal nature of these variants is not yet clear (Wagenstaller et al. 2007; Cukier et al. 2012; Talkowski et al. 2011) MBD5 encodes a protein with a methyl-CpG binding domain that belongs to the same structural family as MeCP2. MBD5 localizes to heterochromatic regions of DNA around centromeres, but has not been shown to bind directly to methylated DNA (Laget et al. 2010). It is proposed that MBD5 directs epigenetic regulation of neuronal gene expression.

Testing Strategy

This test provides full coverage of all coding exons of the MBD5 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing with CNV PG-Select

One study identified a de novo nonsense variant in MBD5 in 1 of 78 (~1%) individuals with moderate to severe intellectual disability of unknown cause (Bonnet et al. 2013).

Indications for Test

MBD5 testing should be considered in patients with clinical features of 2q23.1 deletion syndrome. In addition, MBD5 testing should be considered in patients diagnosed with Angelman, Rett, Smith-Magenis or other clinically overlapping syndromes but for which no genetic cause has been identified (Van Bon et al. 2009).

Gene

Official Gene Symbol OMIM ID
MBD5 611472
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mental Retardation, Autosomal Dominant 1 AD 156200

Citations

  • Bon BW Van, Koolen DA, Brueton L, McMullan D, Lichtenbelt KD, Adès LC, Peters G, Gibson K, Novara F, Pramparo T. 2009. The 2q23. 1 microdeletion syndrome: clinical and behavioural phenotype. European journal of human genetics 18: 163–170. PubMed ID: 19809484
  • Bonnet C, Khan A Ali, Bresso E, Vigouroux C, Béri M, Lejczak S, Deemer B, Andrieux J, Philippe C, Moncla A, Giurgea I, Devignes M-D, et al. 2013. Extended spectrum of MBD5 mutations in neurodevelopmental disorders. European Journal of Human Genetics. PubMed ID: 23422940
  • Cukier HN, Lee JM, Ma D, Young JI, Mayo V, Butler BL, Ramsook SS, Rantus JA, Abrams AJ, Whitehead PL, Wright HH, Abramson RK, et al. 2012. The Expanding Role of MBD Genes in Autism: Identification of a MECP2 Duplication and Novel Alterations in MBD5 , MBD6 , and SETDB1: ASD patients with novel variants in MBD genes. Autism Research 5: 385–397. PubMed ID: 23055267
  • Hodge JC, Mitchell E, Pillalamarri V, Toler TL, Bartel F, Kearney HM, Zou YS, Tan WH, Hanscom C, Kirmani S, Hanson RR, Skinner SA, et al. 2013. Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities. Molecular Psychiatry. PubMed ID: 23587880
  • Kleefstra, T. et al. (2012). "Disruption of an EHMT1-Associated Chromatin-Modification Moduce Causes Intellectual Disability." Am J Hu Genet 91(1):73-82. PubMed ID: 22726846
  • Laget S, Joulie M, Masson F Le, Sasai N, Christians E, Pradhan S, Roberts RJ, Defossez P-A. 2010. The Human Proteins MBD5 and MBD6 Associate with Heterochromatin but They Do Not Bind Methylated DNA. PLoS ONE 5: e11982. PubMed ID: 20700456
  • Mullegama SV, Rosenfeld JA, Orellana C, Bon BWM van, Halbach S, Repnikova EA, Brick L, Li C, Dupuis L, Rosello M, Aradhya S, Stavropoulos DJ, et al. 2013. Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder. European Journal of Human Genetics. PubMed ID: 23632792
  • Talkowski ME, Mullegama SV, Rosenfeld JA, Bon BWM van, Shen Y, Repnikova EA, Gastier-Foster J, Thrush DL, Kathiresan S, Ruderfer DM, Chiang C, Hanscom C, et al. 2011. Assessment of 2q23.1 Microdeletion Syndrome Implicates MBD5 as a Single Causal Locus of Intellectual Disability, Epilepsy, and Autism Spectrum Disorder. The American Journal of Human Genetics 89: 551–563. PubMed ID: 21981781
  • Wagenstaller J, Spranger S, Lorenz-Depiereux B, Kazmierczak B, Nathrath M, Wahl D, Heye B, Gläser D, Liebscher V, Meitinger T, Strom TM. 2007. Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental Retardation. The American Journal of Human Genetics 81: 768–779. PubMed ID: 17847001

Ordering/Specimens

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