Chromosomal imbalance letterA 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
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.
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