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; Eli Sprecher

doi:10.1016/j.ajhg.2009.07.001

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

Research output: Contribution to journal › Article › peer-review

65 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.

Original language	English
Pages (from-to)	254-263
Number of pages	10
Journal	American Journal of Human Genetics
Volume	85
Issue number	2
Early online date	23 Jul 2009
DOIs	https://doi.org/10.1016/j.ajhg.2009.07.001
Publication status	Published - 14 Aug 2009
Externally published	Yes

Access to Document

10.1016/j.ajhg.2009.07.001Licence: Other

Cite this

Basel-Vanagaite, L., Sarig, O., Hershkovitz, D., Fuchs-Telem, D., Rapaport, D., Gat, A., Isman, G., Shirazi, I., Shohat, M., Enk, C. D., Birk, E., Kohlhase, J., Matysiak-Scholze, U., Maya, I., Knopf, C., Peffekoven, A., Hennies, H-C., Bergman, R., Horowitz, M., ... 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

@article{fbc84e603cc44dba8345693926806bd5,

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.",

keywords = "Adolescent, Adult, Alopecia, Carrier Proteins, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 20, Consanguinity, Cutis Laxa, Dermatologic Surgical Procedures, Dermis, Elastic Tissue, Extracellular Matrix Proteins, Frameshift Mutation, Genes, Recessive, Guanine Nucleotide Exchange Factors, Homozygote, Humans, Immunohistochemistry, Phenotype, Radiography, Scoliosis, Skin, Skull, Syndrome, Journal Article",

author = "Lina Basel-Vanagaite and Ofer Sarig and Dov Hershkovitz and Dana Fuchs-Telem and Debora Rapaport and Andrea Gat and Gila Isman and Idit Shirazi and Mordechai Shohat and Enk, {Claes D} and Efrat Birk and J{\"u}rgen Kohlhase and Uta Matysiak-Scholze and Idit Maya and Carlos Knopf and Anette Peffekoven and Hans-Christian Hennies and Reuven Bergman and Mia Horowitz and Akemi Ishida-Yamamoto and Eli Sprecher",

year = "2009",

month = aug,

day = "14",

doi = "10.1016/j.ajhg.2009.07.001",

language = "English",

volume = "85",

pages = "254--263",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "2",

}

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

TY - JOUR

T1 - RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis

T2 - MACS Syndrome

AU - Basel-Vanagaite, Lina

AU - Sarig, Ofer

AU - Hershkovitz, Dov

AU - Fuchs-Telem, Dana

AU - Rapaport, Debora

AU - Gat, Andrea

AU - Isman, Gila

AU - Shirazi, Idit

AU - Shohat, Mordechai

AU - Enk, Claes D

AU - Birk, Efrat

AU - Kohlhase, Jürgen

AU - Matysiak-Scholze, Uta

AU - Maya, Idit

AU - Knopf, Carlos

AU - Peffekoven, Anette

AU - Hennies, Hans-Christian

AU - Bergman, Reuven

AU - Horowitz, Mia

AU - Ishida-Yamamoto, Akemi

AU - Sprecher, Eli

PY - 2009/8/14

Y1 - 2009/8/14

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Alopecia

KW - Carrier Proteins

KW - Case-Control Studies

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 20

KW - Consanguinity

KW - Cutis Laxa

KW - Dermatologic Surgical Procedures

KW - Dermis

KW - Elastic Tissue

KW - Extracellular Matrix Proteins

KW - Frameshift Mutation

KW - Genes, Recessive

KW - Guanine Nucleotide Exchange Factors

KW - Homozygote

KW - Humans

KW - Immunohistochemistry

KW - Phenotype

KW - Radiography

KW - Scoliosis

KW - Skin

KW - Skull

KW - Syndrome

KW - Journal Article

UR - http://www.cell.com/ajhg/home

U2 - 10.1016/j.ajhg.2009.07.001

DO - 10.1016/j.ajhg.2009.07.001

M3 - Article

C2 - 19631308

VL - 85

SP - 254

EP - 263

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 2

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this