Table 1.

Heterozygous Disease-Segregating Mutations Identified Through WES. All Variants Were Absent in Large Number of Control Individuals.

Ch	Position	Gene	Nucleotide change	Protein change	Protein domain	Conservationa	Pathogenicity predictionb	ExAC data (EU fqcy)	Human brain expressionc	Associated mechanisms/diseases
1	31,211,818	LAPTM5	c.479C > T	p.T160I	Mtp (28-261)	High	Deleterious	Not present	Medium	Lysosomal destabilization/ neuroblastomas, PVNS, autoimmune diseases, and lung cancer
1	109,898,020	SORT1	c.512G > C	p.G171A	Vps10p (133-745aa)	High	Deleterious	Not present	High	NPs ligand, lysosomal sorting, endocytosis/ FTD, heart diseases
19	48,946,504	GRIN2D	c.3321T > A	p.D1107E	None	Medium	Neutral	2/15,812	Medium	Schizophrenia

Note. EU fqcy refers to the frequency of the variants in the European population assessed in the ExAC; Mtp refers to Golgi 4-transmembrane spanning transporter.

WES = whole exome sequencing. VPS10p = vacuolar sorting protein 10 p; NPs = neuropeptides; PVNS = pigmented villonodular synovitis; FTD = fronto-temporal dementia; ExAC = Exome Aggregation Consortium.

^aConservation outcomes across different species were taken from the homologene NCBI database (http://www.ncbi.nlm.nih.gov/homologene).

^bPrediction of pathogenicity was determined by the following computational programs (See methods): MutPred, SNPs&Go, Mutation Taster, and SIFT.

^cHuman Brain Expression data were acquired from the Human protein atlas (http://www.proteinatlas.org/).