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-Yamamoto & 1 others Eli Sprecher

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

LanguageEnglish
Pages254-263
Number of pages10
JournalAmerican Journal of Human Genetics
Volume85
Issue number2
Early online date23 Jul 2009
DOIs
Publication statusPublished - 14 Aug 2009
Externally publishedYes

Fingerprint

Skin
Microfibrils
Phenotype
Frameshift Mutation
Elastic Tissue
Chromosomes
Mutation
Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis
Proteins
fibulin

Cite this

Basel-Vanagaite, L., Sarig, O., Hershkovitz, D., Fuchs-Telem, D., Rapaport, D., Gat, A., ... Sprecher, E. (2009). RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis: MACS Syndrome. American Journal of Human Genetics, 85(2), 254-263. https://doi.org/10.1016/j.ajhg.2009.07.001
Basel-Vanagaite, Lina ; Sarig, Ofer ; Hershkovitz, Dov ; Fuchs-Telem, Dana ; Rapaport, Debora ; Gat, Andrea ; Isman, Gila ; Shirazi, Idit ; Shohat, Mordechai ; Enk, Claes D ; Birk, Efrat ; Kohlhase, Jürgen ; Matysiak-Scholze, Uta ; Maya, Idit ; Knopf, Carlos ; Peffekoven, Anette ; Hennies, Hans-Christian ; Bergman, Reuven ; Horowitz, Mia ; Ishida-Yamamoto, Akemi ; Sprecher, Eli. / RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis : MACS Syndrome. In: American Journal of Human Genetics. 2009 ; Vol. 85, No. 2. pp. 254-263.
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Basel-Vanagaite, L, Sarig, O, Hershkovitz, D, Fuchs-Telem, D, Rapaport, D, Gat, A, Isman, G, Shirazi, I, Shohat, M, Enk, CD, Birk, E, Kohlhase, J, Matysiak-Scholze, U, Maya, I, Knopf, C, Peffekoven, A, Hennies, H-C, Bergman, R, Horowitz, M, Ishida-Yamamoto, A & Sprecher, E 2009, 'RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis: MACS Syndrome', American Journal of Human Genetics, vol. 85, no. 2, pp. 254-263. https://doi.org/10.1016/j.ajhg.2009.07.001

RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis : MACS Syndrome. / Basel-Vanagaite, Lina; Sarig, Ofer; Hershkovitz, Dov; Fuchs-Telem, Dana; Rapaport, Debora; Gat, Andrea; Isman, Gila; Shirazi, Idit; Shohat, Mordechai; Enk, Claes D; Birk, Efrat; Kohlhase, Jürgen; Matysiak-Scholze, Uta; Maya, Idit; Knopf, Carlos; Peffekoven, Anette; Hennies, Hans-Christian; Bergman, Reuven; Horowitz, Mia; Ishida-Yamamoto, Akemi; Sprecher, Eli.

In: American Journal of Human Genetics, Vol. 85, No. 2, 14.08.2009, p. 254-263.

Research output: Contribution to journalArticle

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AU - Basel-Vanagaite, Lina

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AU - Birk, Efrat

AU - Kohlhase, Jürgen

AU - Matysiak-Scholze, Uta

AU - Maya, Idit

AU - Knopf, Carlos

AU - Peffekoven, Anette

AU - Hennies, Hans-Christian

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KW - Humans

KW - Immunohistochemistry

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KW - Radiography

KW - Scoliosis

KW - Skin

KW - Skull

KW - Syndrome

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Basel-Vanagaite L, Sarig O, Hershkovitz D, Fuchs-Telem D, Rapaport D, Gat A et al. RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis: MACS Syndrome. American Journal of Human Genetics. 2009 Aug 14;85(2):254-263. https://doi.org/10.1016/j.ajhg.2009.07.001