Whole-exome sequencing in Tricho-rhino-phalangeal syndrome (TRPS) type I in a Korean family

다국어 초록 (Multilingual Abstract)

Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant and monogenic disease. Among three types of TRPS, it is known that TRPS type I and type III are caused by deletions or substitutions in the TRPS1 gene, located on chromosome 8 (8q23.3). Although the mutations in TRPS1 gene are responsible for human TRPS, some cases are not detected by the mutations of TRPS1 gene and several cases are presented with different genetic variations. The present case was a sporadic and without TRPS1 mutation. Therefore, we performed whole-exome sequencing (WES) with one patient and his family (father, mother, and brother) and validated novel mutations using PCR and Sanger sequencing. Through family-based WES, we found the two de novo mutations such as ZNF 134 and EXD 3 genes. Through functional effect prediction using disease association Ensembl database, we propose that the de novo mutation of ZNF134 (p.Ser207Arg) could be one of potential candidate genes for causing TRPS and develope the TRPS phenotype in the present case.

참고문헌 (Reference)

1 Ku CS, "Revisiting Mendelian disorders through exome sequencing" 129 : 351-370, 2011

2 Nan X, "Novel deletion mutation of TRPS1 gene in a Chinese patient of trichorhinophalangeal syndrome type I" 523 : 88-91, 2013

3 Momeni P, "Mutations in a new gene, encoding a zinc-finger protein, cause tricho-rhino-phalangeal syndrome type I" 24 : 71-74, 2000

4 Chen LH, "Mutations in TRPS1 gene in trichorhinophalangeal syndrome type I in Asian patients" 163 : 416-419, 2010

5 Ketting RF, "Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD" 99 : 133-141, 1999

6 Kobayashi H, "Missense mutation of TRPS1 in a family of tricho-rhino-phalangeal syndrome type III" 107 : 26-29, 2002

7 Tommerup N, "Isolation and fine mapping of 16novel human zinc finger-encoding cDNAs identify putative candidate genes for developmental and malignant disorders" 27 : 259-264, 1995

8 Piccione M, "Identification of two new mutations in TRPS 1 gene leading to the tricho-rhino-phalangeal syndrome type I and III" 149A : 1837-1841, 2009

9 Jin HS, "Identification of the rare compound heterozygous variants in the NEB gene in a Korean family with intellectual disability, epilepsy and early-childhood-onset generalized muscle weakness" 59 : 643-647, 2014

10 Zhou S, Jin D, "Identification of a new mutation in TRPS1 gene leading to tricho-rhino-phalangeal syndrome I in a Chinese patient" 40 : 277-278, 2013

11 Cheon CK, "Identification of KMT2D and KDM6A mutations by exome sequencing in Korean patients with Kabuki syndrome" 59 : 321-325, 2014

12 Ludecke HJ, "Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III" 68 : 81-91, 2001

13 Hatamura I, "A nonsense mutation in TRPS1 in a Japanese family with tricho-rhino-phalangeal syndrome type I" 59 : 366-367, 2001