Wilson disease (WD) is an autosomal recessive disorder resulting in pathological progressive copper accumulation in liver and other tissues. The worldwide prevalence (P) is about 30/million, while in Sardinia it is in the order of 1/10 000. However, all of these estimates are likely to suffer from an underdiagnosis bias. Indeed, a recent molecular neonatal screening in Sardinia reported a WD prevalence of 1:2707. In this study, we used a new approach that makes it possible to estimate the allelic frequency (q) of an autosomal recessive disorder if one knows the proportion between homozygous and compound heterozygous patients (the homozygosity index or HI) and the inbreeding coefficient (F) in a sample of affected individuals. We applied the method to a set of 178 Sardinian individuals (3 of whom born to consanguineous parents), each with a clinical and molecular diagnosis of WD. Taking into account the geographical provenance of the parents of every patient within Sardinia (to make F computation more precise), we obtained a q ¼ 0.0191 (F ¼ 7.8 10 4, HI ¼ 0.476) and a corresponding prevalence P ¼ 1:2732. This result confirms that the prevalence of WD is largely underestimated in Sardinia. On the other hand, the general reliability and applicability of the HI approach to other autosomal recessive disorders is confirmed, especially ifone is interested in the genetic epidemiology of populations with high frequency of consanguineous marriages.

The homozygosity index (HI) approach reveals high allele frequency for Wilson disease in the Sardinian population

Gialluisi A;
2013

Abstract

Wilson disease (WD) is an autosomal recessive disorder resulting in pathological progressive copper accumulation in liver and other tissues. The worldwide prevalence (P) is about 30/million, while in Sardinia it is in the order of 1/10 000. However, all of these estimates are likely to suffer from an underdiagnosis bias. Indeed, a recent molecular neonatal screening in Sardinia reported a WD prevalence of 1:2707. In this study, we used a new approach that makes it possible to estimate the allelic frequency (q) of an autosomal recessive disorder if one knows the proportion between homozygous and compound heterozygous patients (the homozygosity index or HI) and the inbreeding coefficient (F) in a sample of affected individuals. We applied the method to a set of 178 Sardinian individuals (3 of whom born to consanguineous parents), each with a clinical and molecular diagnosis of WD. Taking into account the geographical provenance of the parents of every patient within Sardinia (to make F computation more precise), we obtained a q ¼ 0.0191 (F ¼ 7.8 10 4, HI ¼ 0.476) and a corresponding prevalence P ¼ 1:2732. This result confirms that the prevalence of WD is largely underestimated in Sardinia. On the other hand, the general reliability and applicability of the HI approach to other autosomal recessive disorders is confirmed, especially ifone is interested in the genetic epidemiology of populations with high frequency of consanguineous marriages.
Wilson disease; genetic epidemiology; consanguinity; homozygosity index
Gialluisi, A; Incollu, S; Pippucci, T; Lepori, Mb; Zappu, A; Loudianos, G; Romeo, G
File in questo prodotto:
File Dimensione Formato  
9_Gialluisi-et-al_EJHG2013b.pdf

non disponibili

Tipologia: Versione Editoriale (PDF)
Licenza: DRM non definito
Dimensione 322.35 kB
Formato Adobe PDF
322.35 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2125191
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 33
social impact