Elsevier

European Journal of Medical Genetics

Volume 53, Issue 5, September–October 2010, Pages 329-332
European Journal of Medical Genetics

Chromosomal imbalance letter
A de novo 7.9 Mb deletion in 22q13.2→qter in a boy with autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings

https://doi.org/10.1016/j.ejmg.2010.06.004Get rights and content

Abstract

We report a 5-year-old boy with mental retardation, autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings, carrying a 7.9 Mb de novo deletion of chromosome 22q13.2→qter. This region contains the SHANK3, NCAPH2 and CYP2D6 genes which are associated with T-cell immune response. The present case provides evidence that 22q13 deletion syndrome may be associated with immune system dysfunction in addition to neuropsychiatric disorders.

Section snippets

Methods of detection

Karyotyping by GTG banding of the proband and the parents at 550 bands of resolution and high-resolution comparative genomic hybridization (HR-CGH) analysis of DNA by high-density fine-tiling oligonucleotide array (NimbleGen, Madison, WI, USA) were made. The fine-tiling array-CGH has a manufacture-specified resolution of 2 kb.

Chromosomal anomaly

Conventional karyotyping on 20 metaphase cells was performed and revealed a karyotype of 46,XY,del(22)(q13.2) (Fig. 1). Array-CGH analysis identified a deletion of 22q13.2→qter with the first clone locating at 41,675,914 bp on distal 22q13.2 and the last clone locating at 49,589,250 bp on 22q13.33 according to UCSC Genome Browser on Human Mar. 2006 Assembly (Fig. 2).

Method of confirmation

FISH experiments were performed using BAC clones on metaphase cells. The deletion was confirmed by using probes RP11-91O6 (22q11.21) and RP11-232E17 (22q13.33) (Fig. 3). Polymorphic DNA marker analysis was made to determine parental origin of the deletion.

Causative of the phenotype

The parental karyotypes were normal. Polymorphic DNA marker analysis revealed that the deletion was de novo and of paternal origin.

Clinical description

The 5-year-old boy presented with mental retardation, autistic features, epilepsy, developmental delay and atopic dermatitis. He was born at term with a birth weight of 3497 g as the only child of healthy unrelated parents. The mother was 23 years of age and the father was 32 years of age at the time of his birth. There was no family history of autism, epilepsy and immunological or mental disorders. He was found to have hypotonia and gross motor delay postnatally. When examined at 1 year of

Discussion

We have described a patient with autistic features, developmental delay, epilepsy, language impairment, mental retardation, abnormal immunological findings and atopic dermatitis, carrying a 7.9 Mb de novo deletion of chromosome 22q13.2→qter. The patient manifested characteristic features of chromosome 22q13 deletion syndrome or Phelan-McDermid syndrome (OMIM 606232) which has clinical characteristics including large or unusual ears, relatively large hands, full brow, dolichocephaly, ptosis,

Acknowledgements

This work was supported by research grants NSC-96-2314-B-195-008-MY3 and NSC-97-2314-B-195-006-MY3 from the National Science Council, and MMH-E-98004 from Mackay Memorial Hospital, Taipei, Taiwan.

References (13)

  • R. Moessner et al.

    Contribution of SHANK3 mutations to autism spectrum disorder

    Am. J. Hum. Genet.

    (2007)
  • R.J. Andrade et al.

    Pharmacogenomics in drug induced liver injury

    Curr. Drug Metab.

    (2009)
  • D.P. Bogdanos et al.

    Enzymes as target antigens of liver-specific autoimmunity: the case of cytochromes P450s

    Curr. Med. Chem.

    (2008)
  • K. Cusmano-Ozog et al.

    22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay

    Am. J. Med. Genet. C Semin. Med. Genet.

    (2007)
  • C.M. Durand et al.

    Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders

    Nat. Genet.

    (2007)
  • K.M. Gosling et al.

    Defective T-cell function leading to reduced antibody production in a kleisin-β mutant mouse

    Immunology

    (2008)
There are more references available in the full text version of this article.

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