Genome-wide linkage and exome analyses identify variants of HMCN1for splenic epidermoid cyst

Abstract

BackgroundSplenic epidermoid cyst is a benign tumor-like lesion affecting the spleen and sometimes occurs in familial form. The causality of such rare diseases remain challenging, however recently, with the emergence of exome re-sequencing, the genetics of many diseases have been unveiled. In the present study, we performed a combinatorial approach of genome-wide parametric linkage and exome analyses for a moderate-sized Japanese family with frequent occurrence of splenic epidermoid cyst to identify the genetic causality of the disease.MethodsTwelve individuals from the family were subject to SNP typing and exome re-sequencing was done for 8 family members and 4 unrelated patients from Kosovo. Linkage was estimated using multi-point parametric linkage analysis assuming a dominant mode of inheritance. All of the candidate variants from exome analysis were confirmed by direct sequencing.ResultsThe parametric linkage analysis suggested two loci on 1q and 14q with a maximal LOD score of 2.5 . Exome generated variants were prioritized based on; impact on the protein coding sequence, novelty or rareness in public databases, and position within the linkage loci. This approach identified three variants; variants of HMCN1 and CNTN2 on 1q and a variant of DDHD1 on 14q. The variant of HMCN1 (p.R5205H) showed the best co-segregation in the family after validation with Sanger sequencing. Additionally, rare missense variants (p.A4704V, p.T5004I, and p.H5244Q) were detected in three unrelated Kosovo patients. The identified variants of HMCN1 are on conserved domains, particularly the two variants on calcium-binding epidermal growth factor domain.ConclusionsThe present study, by combining linkage and exome analyses, identified HMCN1 as a genetic causality of splenic epidermoid cyst. Understanding the biology of the disease is a key step toward developing innovative approaches of intervention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-014-0115-4) contains supplementary material, which is available to authorized users.

Whole exome sequencing identifies novel candidate mutations in a Chinese family with left ventricular noncompaction

“…Despite other novel mutations in conserved regions of genes not being annotated as deleterious by SIFT, PolyPhe2, LRT and the MutationTaster database analyses, it was revealed that a number of said mutations are associated with cardiac function. In the present study, a mutation in HMCN1 (c.T9776C), which encodes for an extracellular protein belonging to the immunoglobulin superfamily, was annotated as deleterious by PolyPhe2, LRT and the MutationTaster databases (32). Furthermore, HMCN1 has previously been revealed to be predominantly expressed in the vascular endothelial cells of coronary arteries and sparsely expressed in the endocardial endothelium in the mouse heart, which may have an important role in myocardial remodeling following myocardial infarction by affecting cardiac fibroblast migration via TGF-β1 signaling (33).…”

Current Concepts and Evaluation of Uro-Rectal Diseases by Transrectal Ultrasound: A Review

“…Prostate Cancer [107] Perianal Paget's Disease [108] Myxoid Liposarcoma [109] Malignant Fibrous Histiocytoma [110] Hemangiopericytoma [111] Cauda Equina Syndrome [112] Carcinoma of the Cervix [113] Carcinoma of the Vagina [114] Epidermoid Cysts [115] Prader-Willi Syndrome [116] Colorectal Carcinoma [117] Benign Prostate Hyperplasia [118] Microglandular Hyperplasia [119] Adenocarcinoma of Cervix [120] Adenoma Malignum [121] Adenosquamous Carcinoma of Cervix [122] Glassy Cell Carcinoma of Cervix [123] Adenoid Basal Carcinoma of Cervix [124] Adenomyosis [125] Uterine Fibroids [126] Endometrial Polyps [127] Hematoma [128] Fournier's Gangrene [129] Malakoplakia [130] Aneurysmal bone cyst [131] Ewing Sarcoma [132] Osteosarcoma [133] Chondrosarcoma [134] Neurofibroma [135] Neuroblastoma [136] Schwannoma [137] Chordoma [138] Malignant Schwannoma [139] Hemangioma [140] Myelolipoma [141] Leiomyoma [142] Villous Adenoma [143] Solitary Fibrous tumor [144] Castleman disease [145] Lymphoma [146] Gastrointestinal Stromal Tumor [147] Epithielial Malignancies …”