Genetic analysis and prenatal diagnosis of 76 Chinese families with X-linked adrenoleukodystrophy

Mol Genet Genomic Med. 2022 Jan;10(1):e1844. doi: 10.1002/mgg3.1844. Epub 2021 Nov 26.


Background: Variants in the ATP binding cassette protein subfamily D member 1 (ABCD1) gene are known to cause X-linked adrenoleukodystrophy (X-ALD). This study focused on the characteristics of ABCD1 variants in Chinese X-ALD families and elucidated the value of genetic approaches for X-ALD.

Methods: 68 male probands diagnosed as X-ALD were screened for ABCD1 variants by the Sanger sequencing of polymerase chain reaction (PCR) products and multiplex ligation-dependent probe amplification (MLPA) combined with long-range PCR. Prenatal diagnosis was performed in 20 foetuses of 17 probands' mothers. Descriptive statistics were used to summarise the gene variants and prenatal diagnosis characteristics and outcomes.

Results: This study allowed the identification of 61 variants occurring in 68 families, including 58 single nucleotide variants or small deletion/insertion variants and 3 large deletions. Three probands with no variants detected by next-generation sequencing were found to have variants by PCR-sequencing. Prenatal diagnosis found that 10 of the 20 foetuses had no variants in ABCD1.

Conclusion: PCR primers that do not amplify the pseudogenes must be used for PCR-sequencing. MLPA combined with long-range PCR can detect large deletions and insertions, which are usually undetectable by PCR-sequencing. Prenatal diagnosis could help to prevent the birth of infants with X-ALD.

Keywords: ATP binding cassette transporter-subfamily D and member 1; Chinese cohort; adrenoleukodystrophy; prenatal diagnosis.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Adrenoleukodystrophy* / diagnosis
  • Adrenoleukodystrophy* / genetics
  • Asian People / genetics
  • China
  • Female
  • Humans
  • Infant
  • Male
  • Pregnancy
  • Prenatal Diagnosis


  • ATP-Binding Cassette Transporters