干旱区生态环境知识资源中心(Arid): A Novel ATP6V0A2 Mutation Causing Recessive Cutis Laxa with Unusual Manifestations of Bleeding Diathesis and Defective Wound Healing

Arid

DOI	10.4274/tjh.galenos.2018.2018.0325
	A Novel ATP6V0A2 Mutation Causing Recessive Cutis Laxa with Unusual Manifestations of Bleeding Diathesis and Defective Wound Healing
	Karacan, Ilker 1,2; Kucukkaya, Reyhan Diz 3; Karakus, Fatma Nur 4; Solakoglu, Seyhun 4; Tolun, Aslihan 5; Hancer, Veysel Sabri 6; Turanli, Eda Tahir 1,7
通讯作者	Turanli, Eda Tahir
来源期刊	TURKISH JOURNAL OF HEMATOLOGY
ISSN	1300-7777
EISSN	1308-5263
出版年	2019
卷号	36 期号:1 页码:29-36
英文摘要	Objective: Autosomal recessive cutis laxa type IIA (ARCL2A) is a rare congenital disorder characterized by loose arid elastic skin, growth and developmental delay, and skeletal anomalies. It is caused by biallelic mutations in ATP6V0A2. Those mutations lead to increased pH in secretory vesicles and thereby to impaired glycosyltransferase activity and organelle trafficking. We aimed to identify the genetic and molecular cause of the unexpected hematological findings in a Turkish family. Materials and Methods: We performed clinical, genetic, and histological analyses of a consanguineous family afflicted with wrinkled and loose skin, microcephaly, intellectual disability, cleft lip and palate, downslanting palpebral fissures, ectopia lentis, bleeding diathesis, and defective wound healing. Results: Linkage analysis using SNP genotype data yielded a maximal multipoint logarithm of odds score of 2.59 at 12q24.21-24.32. Exome sequence analysis for the proband led to the identification of novel homozygous frameshift c.2085_2088del (p.(Ser695Argfs*12)) in ATP6V0A2, within the linked region, in the two affected siblings. Conclusion: Our patients do not have gross structural brain defects besides microcephaly, strabismus, myopia, and growth or developmental delay. Large platelets were observed in the patients and unusual electron-dense intracytoplasmic inclusions in fibroblasts and epidermal basal cells were observed in both affected and unaffected family members. The patients do not have any genetic defect in the VWF gene but von Willebrand factor activity to antigen ratios were low. Clinical findings of bleeding diathesis and defective wound healing have not been reported in ARCL2A and hence our findings expand the phenotypic spectrum of the disease.
英文关键词	ATP6V0A2 Cutis laxa Wound healing Bleeding diathesis Whole exome sequencing
类型	Article
语种	英语
国家	Turkey
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000458334600005
WOS关键词	MULTIMERIZATION ; GLYCOSYLATION
WOS类目	Hematology
WOS研究方向	Hematology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/219140
作者单位	1.Istanbul Tech Univ, Grad Sch Sci Engn & Technol, Dept Mol Biol Genet & Biotechnol, Istanbul, Turkey; 2.Istanbul Medeniyet Univ, Dept Mol Biol & Genet, Istanbul, Turkey; 3.Istanbul Bilim Univ, Dept Hematol, Fac Med, Istanbul, Turkey; 4.Istanbul Univ, Dept Histol & Embryol, Istanbul Fac Med, Istanbul, Turkey; 5.Bogazici Univ, Dept Mol Biol & Genet, Istanbul, Turkey; 6.Istanbul Bilim Univ, Dept Mol Biol & Genet, Istanbul, Turkey; 7.Istanbul Tech Univ, Dept Mol Biol & Genet, Istanbul, Turkey
推荐引用方式 GB/T 7714	Karacan, Ilker,Kucukkaya, Reyhan Diz,Karakus, Fatma Nur,et al. A Novel ATP6V0A2 Mutation Causing Recessive Cutis Laxa with Unusual Manifestations of Bleeding Diathesis and Defective Wound Healing[J],2019,36(1):29-36.
APA	Karacan, Ilker.,Kucukkaya, Reyhan Diz.,Karakus, Fatma Nur.,Solakoglu, Seyhun.,Tolun, Aslihan.,...&Turanli, Eda Tahir.(2019).A Novel ATP6V0A2 Mutation Causing Recessive Cutis Laxa with Unusual Manifestations of Bleeding Diathesis and Defective Wound Healing.TURKISH JOURNAL OF HEMATOLOGY,36(1),29-36.
MLA	Karacan, Ilker,et al."A Novel ATP6V0A2 Mutation Causing Recessive Cutis Laxa with Unusual Manifestations of Bleeding Diathesis and Defective Wound Healing".TURKISH JOURNAL OF HEMATOLOGY 36.1(2019):29-36.