RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis: MACS Syndrome

Lina Basel-Vanagaite, Ofer Sarig, Dov Hershkovitz, Dana Fuchs-Telem, Debora Rapaport, Andrea Gat, Gila Isman, Idit Shirazi, Mordechai Shohat, Claes D. Enk, Efrat Birk, Jürgen Kohlhase, Uta Matysiak-Scholze, Idit Maya, Carlos Knopf, Anette Peffekoven, Hans Christian Hennies, Reuven Bergman, Mia Horowitz, Akemi Ishida-YamamotoEli Sprecher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)254-263
Number of pages10
JournalAmerican Journal of Human Genetics
Volume85
Issue number2
DOIs
StatePublished - 14 Aug 2009

Fingerprint

Dive into the research topics of 'RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis: MACS Syndrome'. Together they form a unique fingerprint.

Cite this