RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome.
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.
Basel-Vanagaite
Lina
L
Schneider Children's Medical Center of Israel and Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel.
Sarig
Ofer
O
Hershkovitz
Dov
D
Fuchs-Telem
Dana
D
Rapaport
Debora
D
Gat
Andrea
A
Isman
Gila
G
Shirazi
Idit
I
Shohat
Mordechai
M
Enk
Claes D
CD
Birk
Efrat
E
Kohlhase
Jürgen
J
Matysiak-Scholze
Uta
U
Maya
Idit
I
Knopf
Carlos
C
Peffekoven
Anette
A
Hennies
Hans-Christian
HC
Bergman
Reuven
R
Horowitz
Mia
M
Ishida-Yamamoto
Akemi
A
Sprecher
Eli
E
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
D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D020662:Guanine Nucleotide Exchange Factors; C447829:RIN2 protein, human