title: RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome.
abstract: Inherited disorders of elastic tissue represent a complex and heterogeneous group of diseases, characterized often by sagging skin and occasionally by life-threatening visceral complications. In the present study, we report on an autosomal-recessive disorder that we have termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis). The disorder was mapped to chromosome 20p11.21-p11.23, and a homozygous frameshift mutation in RIN2 was found to segregate with the disease phenotype in a large consanguineous kindred. The mutation identified results in decreased expression of RIN2, a ubiquitously expressed protein that interacts with Rab5 and is involved in the regulation of endocytic trafficking. RIN2 deficiency was found to be associated with paucity of dermal microfibrils and deficiency of fibulin-5, which may underlie the abnormal skin phenotype displayed by the patients.
authors.affiliation: Schneider Children's Medical Center of Israel and Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel.
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.forename: Ofer
authors.initials: O
authors.lastname: Sarig
authors.forename: Dov
authors.initials: D
authors.lastname: Hershkovitz
authors.forename: Dana
authors.initials: D
authors.lastname: Fuchs-Telem
authors.forename: Debora
authors.initials: D
authors.lastname: Rapaport
authors.forename: Andrea
authors.initials: A
authors.lastname: Gat
authors.forename: Gila
authors.initials: G
authors.lastname: Isman
authors.forename: Idit
authors.initials: I
authors.lastname: Shirazi
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
authors.forename: Claes D
authors.initials: CD
authors.lastname: Enk
authors.forename: Efrat
authors.initials: E
authors.lastname: Birk
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kohlhase
authors.forename: Uta
authors.initials: U
authors.lastname: Matysiak-Scholze
authors.forename: Idit
authors.initials: I
authors.lastname: Maya
authors.forename: Carlos
authors.initials: C
authors.lastname: Knopf
authors.forename: Anette
authors.initials: A
authors.lastname: Peffekoven
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Hennies
authors.forename: Reuven
authors.initials: R
authors.lastname: Bergman
authors.forename: Mia
authors.initials: M
authors.lastname: Horowitz
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D000293:Adolescent; D000328:Adult; D000505:Alopecia / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D003241:Consanguinity; D003483:Cutis Laxa / Q000235:genetics* / Q000378:metabolism; D062109:Dermatologic Surgical Procedures; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D004547:Elastic Tissue / Q000378:metabolism / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D016368:Frameshift Mutation; D005808:Genes, Recessive; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D010641:Phenotype; D011859:Radiography; D012600:Scoliosis / Q000235:genetics*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012886:Skull / Q000000981:diagnostic imaging / Q000254:growth & development*; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D020662:Guanine Nucleotide Exchange Factors; C447829:RIN2 protein, human