A Family with γ-Thalassemia and High Hb A2 Levels

Autor:	Rita Selvatici, Maria Pia Cappabianca, Alessandra Ferlini, Marina Taddei Masieri, Paola Rimessi, Anna Venturoli, Bernadetta Dolcini, Stefania Bigoni, Anna Ravani, Giulia Parmeggiani, Francesca Gualandi
Rok vydání:	2016
Předmět:	Proband Adult Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Thalassemia Clinical Biochemistry Gene Dosage Mean corpuscular hemoglobin Biology NO 03 medical and health sciences globin gene deletion 0302 clinical medicine Intergenic region hemic and lymphatic diseases Gene cluster medicine Humans gamma-Globins Hemoglobin A2 Mean corpuscular volume Gene Genetics (clinical) Sequence Deletion g-Thalassemia (g-thal) genetic counseling globin gene deletion high Hb A2 level Genetics genetic counseling medicine.diagnostic_test high Hb A2 level Biochemistry (medical) Hematology medicine.disease Pedigree Gene Expression Regulation 030220 oncology & carcinogenesis Medical genetics Female g-Thalassemia (g-thal) 030215 immunology
Zdroj:	Hemoglobin. 40(3)
ISSN:	1532-432X
Popis:	We describe a family carrying a γ-globin gene deletion associated with an increase of Hb A2 level beyond the normal range. The family included the proband, his sister and their father, all with increased Hb A2 and normal Hb F levels. The proband and his sister showed borderline values of mean corpuscular volume (MCV) and reduced values of mean corpuscular hemoglobin (Hb) (MCH). The proband was referred to our Medical Genetics Service for preconception counseling together with his partner, a typical β-thalassemia (β-thal) carrier. The results were negative for the most frequent α-thalassemia (α-thal) mutations, and had no significant sequence variations of the coding sequences and promoter of the β- and δ-globin genes. Quantitative analysis by multiplex ligation-dependent probe amplification (MPLA) of the β-globin gene cluster detected a heterozygous deletion, ranging between 2.1 and 4.7 kb, in the proband, his sister and the father. The deletion involved the (G)γ gene and (G)γ-(A)γ intergenic region, whereas the 3' region of the (A)γ gene was preserved. A subsequent gap-polymerase chain reaction (gap-PCR) showed that a hybrid (GA)γ fusion gene was present. The deletion segregated with the elevation of Hb A2. The MLPA analysis of the β-globin gene cluster in 150 control alleles excluded a common polymorphism. Despite stronger evidence being needed, the described family suggests a possible role of this γ-globin gene deletion in contributing to Hb A2 elevation, possibly by altering the transcription regulation of the cluster. We propose γ-globin gene dosage analysis to be performed in patients with unexplained elevated Hb A2 levels.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2437a91c7035e0ea3ac5b87aa43063dd https://pubmed.ncbi.nlm.nih.gov/27117568 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.