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

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. A retrospective study was conducted using the medical records of 76 families with X‐ALD in China, presenting the ABCD1 gene variant spectrum in a large Chinese cohort. The results of this study indicate that MLPA and long‐range PCR should be considered in routine molecular diagnostics for patients with X‐ALD, as a complement to PCR‐sequencing. This single centre study was presented as a cross‐sectional study, and a prospective and multicentre study with a larger sample size would be more convincing.