Editing Adrenoleukodystrophy (section)

==Genetics==
[[File:ABCD1-gene.svg|220px|right]]
ALD is caused by mutations in ''ABCD1'', located at [[X chromosome|Xq28]] and demonstrates [[X-linked recessive]] inheritance. The gene ''ABCD1'' encodes a peroxisomal membrane transporter which is responsible for transporting very long chain fatty acid substrate into the peroxisomes for degradation. Mutations in this gene that interfere with this process cause this syndrome.<ref name=Hung2013>{{cite journal |last1=Hung |first1=Kun-Long |last2=Wang |first2=Jinn-Shyan |last3=Keng |first3=Wee Teik |last4=Chen |first4=Hui-Ju |last5=Liang |first5=Jao-Shwann |last6=Ngu |first6=Lock Hock |last7=Lu |first7=Jyh-Feng |title=Mutational Analyses on X-Linked Adrenoleukodystrophy Reveal a Novel Cryptic Splicing and Three Missense Mutations in the ABCD1 Gene |journal=Pediatric Neurology |date=September 2013 |volume=49 |issue=3 |pages=185–190 |doi=10.1016/j.pediatrneurol.2013.04.021 |pmid=23835273 }}</ref>

Males with an ''ABCD1'' mutation are [[hemizygote|hemizygous]], as they only have a single X chromosome. Female carriers will typically avoid the most severe manifestations of the disease, but often become symptomatic later in life.<ref name=scriver/> Although the detection of an ''ABCD1'' mutation identifies an individual who is affected with a form of ALD, there is no [[genotype–phenotype correlation]].<ref name=geno>{{cite journal |last1=Smith |first1=Kirby D. |last2=Kemp |first2=Stephan |last3=Braiterman |first3=Lelita T. |last4=Lu |first4=Jyh-Feng |last5=Wei |first5=He-Ming |last6=Geraghty |first6=Michael |last7=Stetten |first7=Gail |last8=Bergin |first8=James S. |last9=Pevsner |first9=Jonathan |last10=Watkins |first10=Paul A. |title=X-linked adrenoleukodystrophy: Genes, mutations, and phenotypes |journal=Neurochemical Research |date=1999 |volume=24 |issue=4 |pages=521–535 |doi=10.1023/a:1022535930009 |pmid=10227685 |s2cid=38326524 }}</ref> Within a family, there will often be several different phenotypes, despite the presence of the same causative mutation. In one case, a family with six affected members displayed five different phenotypes.<ref name=scriver/> There are no common mutations that cause ALD, most are private or familial.  Almost 600<ref name=genereviews/> different mutations have been identified, approximately half are [[missense mutations]], one quarter are [[frameshift mutation|frameshifts]], with in-frame deletions and splicing defects making up the remainder.<ref name=scriver/> The incidence of new mutations in ALD (those occurring spontaneously, rather than being inherited from a carrier parent) is estimated at 4.1%, with the possibility that these are due to [[germline mosaicism]].<ref name=genereviews/>