TY - JOUR
T1 - SLITRK6 mutations cause myopia and deafness in humans and mice
AU - Tekin, Mustafa
AU - Chioza, Barry A.
AU - Matsumoto, Yoshifumi
AU - Diaz-Horta, Oscar
AU - Cross, Harold E.
AU - Duman, Duygu
AU - Kokotas, Haris
AU - Moore-Barton, Heather L.
AU - Sakoori, Kazuto
AU - Ota, Maya
AU - Odaka, Yuri S.
AU - Foster, Joseph
AU - Cengiz, F. Basak
AU - Tokgoz-Yilmaz, Suna
AU - Tekeli, Oya
AU - Grigoriadou, Maria
AU - Petersen, Michael B.
AU - Sreekantan-Nair, Ajith
AU - Gurtz, Kay
AU - Xia, Xia Juan
AU - Pandya, Arti
AU - Patton, Michael A.
AU - Young, Juan I.
AU - Aruga, Jun
AU - Crosby, Andrew H.
PY - 2013/5/1
Y1 - 2013/5/1
N2 - Myopia is by far the most common human eye disorder that is known to have a clear, albeit poorly defined, heritable component. In this study, we describe an autosomal-recessive syndrome characterized by high myopia and sensorineural deafness. Our molecular investigation in 3 families led to the identification of 3 homozygous nonsense mutations (p.R181X, p.S297X, and p.Q414X) in SLIT and NTRK-like family, member 6 (SLITRK6), a leucine-rich repeat domain transmembrane protein. All 3 mutant SLITRK6 proteins displayed defective cell surface localization. High-resolution MRI of WT and Slitrk6-deficient mouse eyes revealed axial length increase in the mutant (the endophenotype of myopia). Additionally, mutant mice exhibited auditory function deficits that mirrored the human phenotype. Histological investigation of WT and Slitrk6-deficient mouse retinas in postnatal development indicated a delay in synaptogenesis in Slitrk6-deficient animals. Taken together, our results showed that SLITRK6 plays a crucial role in the development of normal hearing as well as vision in humans and in mice and that its disruption leads to a syndrome characterized by severe myopia and deafness.
AB - Myopia is by far the most common human eye disorder that is known to have a clear, albeit poorly defined, heritable component. In this study, we describe an autosomal-recessive syndrome characterized by high myopia and sensorineural deafness. Our molecular investigation in 3 families led to the identification of 3 homozygous nonsense mutations (p.R181X, p.S297X, and p.Q414X) in SLIT and NTRK-like family, member 6 (SLITRK6), a leucine-rich repeat domain transmembrane protein. All 3 mutant SLITRK6 proteins displayed defective cell surface localization. High-resolution MRI of WT and Slitrk6-deficient mouse eyes revealed axial length increase in the mutant (the endophenotype of myopia). Additionally, mutant mice exhibited auditory function deficits that mirrored the human phenotype. Histological investigation of WT and Slitrk6-deficient mouse retinas in postnatal development indicated a delay in synaptogenesis in Slitrk6-deficient animals. Taken together, our results showed that SLITRK6 plays a crucial role in the development of normal hearing as well as vision in humans and in mice and that its disruption leads to a syndrome characterized by severe myopia and deafness.
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U2 - 10.1172/JCI65853
DO - 10.1172/JCI65853
M3 - Article
C2 - 23543054
AN - SCOPUS:84877101612
SN - 0021-9738
VL - 123
SP - 2094
EP - 2102
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 5
ER -