PARK2 copy number aberrations in two children presenting with autism spectrum disorder

2011-06-02 14:44:09

American Journal of Medical Genetics Part B; 2011 June; 156(4):413-20

Angela Scheuerle and Kathleen Wilson


Autism spectrum disorder (ASD) comprises a defined set of aberrant behavioral signs and symptoms that have a multitude of potential causes. Being a symptom complex rather than a specific diagnosis, patients with ASD have been found to have single gene mutations as well as cytogenetic aberrations identified by conventional analysis and fluorescence in situ hybridization (FISH). The more recent technology of cytogenomic microarray analysis (CMA) has identified an increasing number of copy number gains and losses present in patients with ASD [Cook and Scherer, 2008; Glessner et al., 2009; Colak et al., 2011] In 2009, Glessner et al. identified seven patients with ASD who had a chromosome 6 copy number loss involving the PARK2 gene region. Control patients did not show this copy number loss. To our knowledge, there are no reports of ASD with duplication of PARK2. Reported here are two cases of males with ASD who were found to have copy number aberrations involving the PARK2 gene, one with deletion and one with duplication.

Case Reports

Patient #1

This was a male patient seen at 14 years, 4 months with a referral diagnosis of Asperger syndrome. He was delivered at 36 weeks to a 27-year-old G2P0-1EAb1 mother. The pregnancy was complicated by preterm labor in the third trimester. Ultrasounds were normal. Amniocentesis karyogram was normal male: 46,XY. (Testing was done because mother's previous pregnancy resulted in a fetus with 45,X.) Birth weight was 2,950g. Birth length was 50cm. There were no neonatal problems.

Mother had concerns from infancy. The patient had vocal cord nodules removed and had a persistently hoarse voice. He had a frenulectomy and was to have periodontal surgery. He fractured an ankle in a fall. His general health had been good. There had been no hospitalizations. He was on numerous psychotropic medications to treat attention deficit disorder and a diagnosis of Asperger syndrome: methylphenidate, duloxetine, and aripiprazole. His hearing and sight were normal. He was noted to have minimal sleep need and would not sleep without medications mirtazapine and clonazepam. He had somniloquy. His diet was varied, but consisted largely of carbohydrates and fried foods. His activity level was low.

At 14 years, 4 months of age, he was in 8th grade regular and so called Gifted and Talented classes in public school. He was anticipated to graduate early with plans to attend college. He was in a social skills class. He had been discharged from speech therapy. Other than the mother's first pregnancy, there was no family history of birth defects, cognitive impairment, or pregnancy losses.

His weight was 84kg (98th centile). Height was 165cm (50th centile). Head circumference was 56.5cm (75th centile). (Fig. 1). He was brachycephalic. He had nystagmus on lateral and particularly lateral upward gaze. His eyes were deeply set with long, horizontal palpebral fissures. The eyelashes were long. He had upturned ear lobes. His oropharynx was normal. He had a hoarse voice. His cardiovascular and pulmonary exams were unremarkable. He had a symmetric chest and a dowager hump. Visceral exam was limited by obesity. He was a circumcised Tanner I–II male with a buried penis. The left testis was descended. The right testis was not palpable. There was no pubic hair. His extremities were symmetric with tapered fingers and short 4th metacarpals. His feet were normal as were the creasing patterns and nails. He had multiple dark nevi and striae on his trunk. He was generally hypotonic with a hoarse voice, though his articulation was good. There was no tremor or ataxia. He was cooperative with the exam, but acted younger than his stated age.

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