Interstitial deletion of 1p22.2p31.1 and medium-chain acyl-CoA dehydrogenase deficiency in a patient with global developmental delay

Gustavo H.B. Maegawa, Nicola K. Poplawski, Brage Storstein Andresen, Simon E. Olpin, Gloria Nie, Joe T.R. Clarke, Ikuko Teshima

Research output: Contribution to journalArticle

Abstract

We report on a 6-year-old girl who presented at 6 months of age with seizures, delayed psychomotor development and mild facial dysmorphism. A small muscular ventricular septal defect was documented on echocardiogram and brain MRI showed a frontal brain anomaly. Urine organic acid analysis revealed dicarboxylic aciduria, and plasma acylcarnitine analysis showed marked elevation of octanoyl (C8) and decanoyl (C10) carnitines with C8:C10 ratio of 9:1. These results were indicative of medium chain acyl-CoA dehydrogenase deficiency. ACADM gene sequencing showed an apparent homozygous c.166G > C (Ala31Pro) missense mutation in exon 3; however, only the mother was found to be a carrier of this novel missense mutation. This finding along with non-regressive developmental delay prompted further karyotype and genomic investigations. An interstitial deletion of chromosome 1 was detected by repeat G-banding: 46,XX,del(1)(p22. 2p31.1). Parental karyotypes were normal. The deletion was characterized by array CGH analysis using a 1 Mb BAC/PAC array platform. Clones deleted extended from RP11-88B10 (1p31.1) to RP5-1007M22 (1p22.2), a 15.5 Mb deletion which includes the ACADM locus. Clinical review of 6/7 cases of interstitial deletions with breakpoints of 1p22 and 1p31/32, including the patient in this report, indicate a variable phenotype. Thus, although G-band breakpoints are similar, common breakpoints for these alterations are unlikely. This is the first report of a patient with fatty acid oxidation defect caused by a mutation in combination with an interstitial chromosomal deletion.

Original languageEnglish (US)
Pages (from-to)1581-1586
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume146
Issue number12
DOIs
StatePublished - Jun 15 2008

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Keywords

  • Chromosome 1
  • Interstitial deletion
  • Medium-chain acyl-CoA dehydrogenase deficiency

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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