Integration of multicentre data to further characterise the phenotypes of rare clinically significant haemoglobinopathy mutations.

The haemoglobinopathies are common inherited disorders. Although the majority are caused by a small number of frequently occurring mutations, many rare mutations collectively contribute considerably to the clinical burden. Population screening to document genotype and allele frequencies, availability of high throughput technologies, advances in the lower income countries and antenatal screening programmes has led to an increase in data accumulation. However, phenotype data on rare mutations often remains inadequate and based on a single report. A standard system for collecting and reporting genotype and phenotype for rare mutations would assist in clinical management of patients and couples at-risk. We report collective phenotype data for a number of relatively rare mutations identified in long established haemoglobinopathy referral laboratories in three countries. For example, the Codon 22 (C>T) and codon 108 (C>A) alpha2 globin gene mutations have only been reported on single patients.We present data on eight heterozygous/ compound heterozygous patients for each mutation. The alpha1 globin gene codon 108/109(-C) mutation has no documented phenotype data. We present data for seven heterozygous patients. The IVS2-478 (C-A) beta-globinmutation has been reported once in the literature whilst data for fourteen patients are presented. We describe the previously unreported phenotype for compound heterozygous patients for the deletion of HS-40 regulatory element/alpha3.7 deletion, alpha3.7 deletion/alpha3.5 deletion, alpha2 cd22(C>T) /alpha2 cd59(G>A), cd59(G>A) /Hb Constant Spring and Hb Phnom Penh/-SEA. The collective data presented here updates phenotype data significantly and demonstrates the value of combining the experience of multiple laboratories.