A new deletional α‐thalassemia detected in yemenites with hemoglobin H disease

Abstract

A new large deletion from the human alpha-globin gene cluster is characterized. It involves at least 39 kb and includes the two alpha-globin genes, the theta 1-gene, all the pseudogenes, and the two hypervariable regions (HVRs), interzeta-HVR and alpha-globin 3'HVR. The conserved zeta-globin gene has been identified in various restriction fragments of abnormal size. The new deletion was found in four unrelated Israeli patients with Hb H disease, all originating in Yemen, and has been designated--YEM. It is the only two-gene deletion identified in this ethnic group.

Alpha Thaiassermia Genes in Israel: Deletional and Nondeletional Mutations in Patients of Various Origins

“…Throughout their long history in these coun tries, many Jewish communities have main tained relations with their non-Jewish neigh bors as well as with Jews in other parts of the world. With this historic background, the gea-Thalassemia Mutations in Israel Hum Hcrcd 1996;46: [15][16][17][18][19]netic diversity observed in these subjects is not unexpected. Apart from the 3.7 kb rightward deletion, the Mediterranean deletion, the poly(A)-signal mutation and Hb PT have been identified in Middle Eastern Jews.…”

“…Twenty-two of these sub jects had Hb H disease. Thirteen patients were Arabs and 34 were Jews originating from Yemen (12) DNA was prepared from peripheral blood leuko cytes and gene deletions were determined by Southern blot analysis, using a-or ([-globm-specific probes [16]. DNA samples in which no deletion was identified were digested by Hph\ and Nco\ and hybridized with an aglobin probe to detect mutations at the IVS1 splice junction and at the initiation codon, respectively.…”

“…Yet a-thalassemia has been found at a moderately high rate only in Iraqi and Yemenite Jews and in the Arab population [13,14]. Former studies have revealed two new mutations in Israeli a-thalassemia pa tients: a C-»A point mutation on the apglobin gene, which gives rise to production of the unstable Hb Petah Tikva, aaPT [15], and a deletion of 39 kb (or longer) that includes the two a-globin genes, -YEM [16]. In this study, the molecular basis for a-thalassemia in 47 unrelated patients has been characterized.…”

Hemoglobin H disease: not necessarily a benign disorder

“…These are known as "deletional Hb H disease." 11,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] In a smaller proportion of patients, Hb H disease is caused by a deletion removing both ␣-globin genes on one chromosome 16, plus an ␣ ϩ -thalassemia point mutation, or small insertion/deletion, involving either the ␣2-or ␣1-globin gene on the other chromosome 16. These are collectively labeled as the "nondeletional Hb H disease."…”

Type 1 Diabetes Environmental Factors and Correspondence Analysis of HLA Class II Genes in the Yemenite Jewish Community in Israel

“…Our results support the finding of Bonne-Tamir et al (20) that Yemenite Jews differ by gene clustering from all other Jews. The unique genetic background of this ethnic group is supported by its unusually high incidence of autosomal dominant benign neutropenia (21), ␣-thalassemia with specific deletion in the ␣-globin gene (22), and phenylketonuria with specific mutation in the phenylalanine hydroxylase gene (23), as well as an exceptionally low incidence of familial Mediterranean fever (24), glucose-6-phosphate dehydrogenase deficiency (25), and cystic fibrosis (26).…”