Division of Molecular Genetics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada.
Am J Med Genet A. 2010 Jul;152A(7):1808-11. doi: 10.1002/ajmg.a.33462.
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is an autosomal recessive disorder affecting mitochondrial fatty acid oxidation due to mutations in the HADHA gene. We report on a 22-month-old child who was identified on expanded newborn screening with an abnormal acylcarnitine pattern and increased C14OH. Molecular analysis showed that the child was homozygous for the common mutation, c.1526G > C (p.Glu510Gln) in the HADHA gene. Carrier testing on the parental samples revealed that the father was heterozygous for the mutation whereas the mother did not carry the mutation. Short tandem repeat testing with markers covering both short and long arms of chromosome 2 showed that the child has paternal uniparental isodisomy. We highlight the importance of parental testing in cases of homozygosity in autosomal recessive disorders and its impact on genetic counseling of the family.
长链 3-羟酰基辅酶 A 脱氢酶缺乏症是一种常染色体隐性遗传疾病，由于 HADHA 基因突变，影响线粒体脂肪酸氧化。我们报告了一例 22 个月大的患儿，该患儿在扩大的新生儿筛查中发现酰基肉碱图谱异常和 C14OH 增加。分子分析显示，患儿为 HADHA 基因中常见突变 c.1526G > C（p.Glu510Gln）的纯合子。对父母样本的携带者检测显示，父亲为该突变的杂合子，而母亲未携带该突变。覆盖染色体 2 短臂和长臂的短串联重复检测显示，患儿存在父源单亲二体性。我们强调了在常染色体隐性遗传疾病中纯合子病例进行父母检测的重要性及其对家庭遗传咨询的影响。
