Abstract
Biallelic variants in the transmembrane O-mannosyltransferase targeting cadherins 3 (TMTC3) gene have been reported to cause two distinct types of neuron migration defect diseases, known as cobblestone lissencephaly (COB) and periventricular nodular heterotopia (PVNH), combined with intellectual disability and nocturnal seizures. The aim of the current study was to identify the genetic cause of a 22-month-old Chinese boy who presented with white matter plaques, a small frontal lobe, myelin dysplasia, microcephaly, psychomotor delay, language development delay, truncal hypotonia, intractable epilepsy, infantile spasm and bilateral single transverse palmar creases. Whole-exome sequencing revealed novel heterozygous variant compounds in the TMTC3 gene (c.1123G>A, p.Glu375Lys and c.1126_1129del, p.Arg376Tyrfs*13). Most of the clinical features of the patient are consistent with COB. However, the deformities in the brain (white matter plaques, small frontal lobe and myelin dysplasia) in the patient were more severe compared with those generally exhibited by PVNH, but less severe compared with those presented by COB. Moreover, the patient exhibited bilateral single transverse palmar creases, which, to the best of our knowledge, have not been described previously in patients with a TMTC3 variation. In summary, the current study reported a pediatric Chinese patient with COB-like syndrome caused by TMTC3 gene variations. The present results indicated that variation in the TMTC3 gene can lead to highly variable clinical phenotypes.