title: X-linked elliptocytosis with impaired growth is related to mutated AMMECR1.
abstract: In this study, we report a family with X-linked recessive syndrome caused by mutated AMMECR1 and characterized by elliptocytosis with or without anemia, midface hypoplasia, proportionate short stature and hearing loss. Recently, mutations in AMMECR1 were reported in two maternal half-brothers, presenting with nephrocalcinosis, midface hypoplasia and, in one of the siblings, deafness and elliptocytosis. AMMECR1 gene is localized in the critical region of contiguous deletion syndrome on Xq22.3 implicated in Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis (AMME complex). Interestingly, alternative splicing of exon 2, the same exon harboring the truncating mutation, was observed in the proband and in his unaffected mother. Alternative splicing of this exon is predicted to lead to an in-frame deletion. We provide further evidence that mutated AMMECR1 gene is responsible for this clinically recognizable X-linked condition with variable expressivity.
authors.affiliation: Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel; Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel. Electronic address: basel@post.tau.ac.il.
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Pillar
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Isakov
authors.affiliation: Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Israel.
authors.forename: Pola
authors.initials: P
authors.lastname: Smirin-Yosef
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Irina
authors.initials: I
authors.lastname: Lagovsky
authors.affiliation: Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel; Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Orenstein
authors.affiliation: Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Israel.
authors.forename: Mali
authors.initials: M
authors.lastname: Salmon-Divon
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Hematology Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
authors.affiliation: Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
authors.forename: Tami
authors.initials: T
authors.lastname: Zaft
authors.affiliation: Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
authors.forename: Lily
authors.initials: L
authors.lastname: Bazak
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Meyerovitch
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Pelli
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Botchan
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Luba
authors.initials: L
authors.lastname: Farberov
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Daphna
authors.initials: D
authors.lastname: Weissglas-Volkov
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: nshomron@post.tau.ac.il.
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
mesh_terms: D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004612:Elliptocytosis, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017353:Gene Deletion; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009394:Nephritis, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C118927:AMMECR1 protein, human; D011506:Proteins
keywords: AMMECR1 gene; Elliptocytosis; Genomics; X-linked