Exome sequencing in a Chinese family reveals TTC9 mutation associated with keratitis-ichthyosis-deafness (KID) syndrome

Clinical, etiopathogenic, and therapeutic aspects ofKIDsyndrome

“…KID syndrome is genetically heterogeneous and in the most cases are caused by heterozygous germline missense mutation in GJB2 gene, 1‐7,11 which encode the closely related gap junction β‐2 protein (connexins 26) ( 1,4,6 ). Additionally, two heterozygous nonsynonymous mutations p.Asp50Asn in GJB2 and p.Glu162Asp in TTC9 gene were identified in two affected family members proposing new etiological cause 14 …”

“…This hereditary cornification disorder is of unknown prevalence, and to date, 100 cases of KID syndrome have been reported in the literature. 3,6,7,11,14 Inheritance is usually sporadic, but some familial forms have been reported with autosomal dominant and recessive transmission pattern. 1,3,4,6,7,10,14 KID syndrome is genetically heterogeneous and in the most cases are caused by heterozygous germline missense mutation in GJB2 gene, [1][2][3][4][5][6][7]11 which encode the closely related gap junction β-2 protein (connexins 26) ( 1,4,6 ).…”

“…Glu162Asp in TTC9 gene were identified in two affected family members proposing new etiological cause. 14 Connexins are integral membrane proteins forming gap junction channels for diffusional exchange of ions and other metabolites between cells, 6 and play part in a variety of biological functions that allow for intercellular communication between epithelial cells, cell growth and development, 2,3,11 and an expressed in keratinocytes and in support cells of the inner ear. 12 Connexins present a common structure consisting of four transmembrane domains, linked by one cytoplasmic, and two extracellular loops (namely, EC1, and EC2, respectively), with both cytoplasmic Nterminal and C-terminal.…”

“…This hereditary cornification disorder is of unknown prevalence, and to date, ~100 cases of KID syndrome have been reported in the literature 3,6,7,11,14 . Inheritance is usually sporadic, but some familial forms have been reported with autosomal dominant and recessive transmission pattern 1,3,4,6,7,10,14 .…”

“…1 Keratitis-ichthyosis-deafness (KID syndrome, OMIM 148210 and 242150), [1][2][3][4][5][6][7] was initially described by Burns in 1915, 1,2,8 and the acronym is proposed by Skinner et al, in 1981. 1,2,7,9 KID syndrome is a rare congenital disorder characterized by the association of the classic triad of chronic vascularizing keratitis, ichthyosiform erythroderma, and moderate to profound bilateral prelingual sensorineural hearing loss, [1][2][3][4][5][6][7][10][11][12][13][14] which often impacts speech. 11…”