title: Molecular study of six families originating from the Middle-East and presenting with autosomal recessive osteopetrosis.
abstract: Autosomal recessive osteopetrosis is a severe hereditary bone disease whose cellular basis is in the osteoclast, but with heterogeneous molecular defects. We hereby report the clinical and the molecular study of seven patients affected by the recessive form of osteopetrosis (ARO) from six families originating from the Middle-East: four from Lebanon and two from Syria. Parental consanguinity was found in five families. The mean age of diagnosis was 3 months. Failure to thrive, prominent forehead, exophthalmia, optic atrophy, hepatosplenomegaly, neurological manifestations, anaemia, thrombocytopenia, hypocalcaemia, elevated hepatic enzymes and acid phosphatase, and an early fatal outcome were common. Macrocephaly, strabismus, and brain malformations were relatively less common. Mutations were identified in two genes: TCIRG1 and OSTM1. Phenotype-genotype correlation is discussed.
authors.affiliation: Unité de Génétique Médicale, Laboratoire de Biologie Moléculaire et Cytogénétique, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon.
authors.forename: Noëlle
authors.initials: N
authors.lastname: Souraty
authors.forename: Peter
authors.initials: P
authors.lastname: Noun
authors.forename: Claudia
authors.initials: C
authors.lastname: Djambas-Khayat
authors.forename: Eliane
authors.initials: E
authors.lastname: Chouery
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pangrazio
authors.forename: Anna
authors.initials: A
authors.lastname: Villa
authors.forename: Gérard
authors.initials: G
authors.lastname: Lefranc
authors.forename: Annalisa
authors.initials: A
authors.lastname: Frattini
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
mesh_terms: D001483:Base Sequence; D003241:Consanguinity; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D007223:Infant; D007861:Lebanon; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010022:Osteopetrosis / Q000201:enzymology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics; D013593:Syria; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; C489946:OSTM1 protein, human; C472421:TCIRG1 protein, human; D044767:Ubiquitin-Protein Ligases; D025262:Vacuolar Proton-Translocating ATPases