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

被引：57

作者：

Basel-Vanagaite, Lina ^{[1
,2
,3
]}

Sarig, Ofer ^{[5
]}

Hershkovitz, Dov ^{[7
,8
]}

Fuchs-Telem, Dana ^{[1
,5
]}

Rapaport, Debora ^{[4
]}

Gat, Andrea ^{[6
]}

Isman, Gila ^{[5
]}

Shirazi, Idit ^{[5
]}

Shohat, Mordechai ^{[1
,2
,3
,13
]}

Enk, Claes D. ^{[11
]}

Birk, Efrat ^{[1
]}

Kohlhase, Juergen ^{[12
]}

Matysiak-Scholze, Uta ^{[12
]}

Maya, Idit ^{[2
,3
]}

Knopf, Carlos ^{[10
]}

Peffekoven, Anette ^{[13
]}

Hennies, Hans-Christian ^{[13
]}

Bergman, Reuven ^{[9
]}

Horowitz, Mia ^{[4
]}

Ishida-Yamamoto, Akemi ^{[14
]}

Sprecher, Eli ^{[1
,5
,7
]}

机构：

[1] Tel Aviv Univ, Sackler Fac Med, IL-69978 Ramat Aviv, Israel

[2] Schneider Childrens Med Ctr Israel, IL-49100 Petah Tiqwa, Israel

[3] Rabin Med Ctr, Raphael Recanati Genet Inst, IL-49100 Petah Tiqwa, Israel

[4] Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Ramat Aviv, Israel

[5] Tel Aviv Sourasky Med Ctr, Dept Dermatol, IL-64289 Tel Aviv, Israel

[6] Tel Aviv Sourasky Med Ctr, Dept Pathol, IL-64289 Tel Aviv, Israel

[7] Technion Israel Inst Technol, Rappaport Inst, Ctr Translat Genet, IL-31096 Haifa, Israel

[8] Meyer Childrens Hosp, Dept Pathol, IL-31096 Haifa, Israel

[9] Meyer Childrens Hosp, Dept Dermatol, IL-31096 Haifa, Israel

[10] Meyer Childrens Hosp, Metab Dis Unit, IL-31096 Haifa, Israel

[11] Hadassah Hebrew Univ, Sch Med, Dept Dermatol, IL-91120 Jerusalem, Israel

[12] Ctr Human Genet, D-79100 Freiburg, Germany

[13] Univ Cologne, Cologne Ctr Genom, Div Dermatogenet, D-50674 Cologne, Germany

[14] Asahikawa Med Coll, Dept Dermatol, Asahikawa, Hokkaido 0788510, Japan

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2009年 / 85卷 / 02期

关键词：

NUCLEOTIDE EXCHANGE FACTOR; EHLERS-DANLOS-SYNDROME; OF-THE-LITERATURE; SMALL GTPASE RAB5; GAPO SYNDROME; SIBLINGS; GENE; MUTATIONS; ALSIN; ENDOCYTOSIS;

D O I：

10.1016/j.ajhg.2009.07.001

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：254 / 263

页数：10

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