Table 3.

Selected studies using exome and whole genome sequencing for non-cardiovascular disease gene identification.

Disease	Inheritance model	Sequenced subjects	Putative loci identified	Validation	Reference
Exome sequencing projects
Carnevale, Malpuech, Michels, and oculo-skeletal- abdominal syndromes	Autosomal recessive	One proband	MASP1	Co-segregation in two additional families	59
Charcot-Marie-Tooth neuropathy	Autosomal recessive	Two affected family members	GJB1	Co-segregation in the family	60
Congenital chloride losing diarrhea*	Autosomal recessive	One proband with suspected Bartter syndrome	SLC26A3	Sanger sequencing identification of homozygous variants in SLC26A3 in 5 of 39 unrelated patients with suspected Bartter syndrome; clinical followup demonstrating evidence of chloride losing diarrhea	61
FADD deficiency	Autosomal recessive	One proband with biological features of ALPS	FADD	Co-segregation in the family; In vitro assay of FADD protein levels and apoptotic activity	62
Familial amyotrophic lateral sclerosis	Autosomal dominant	Two affected individuals	VCP	Sanger sequencing of a cohort of 210 familial ALS cases	63
Familial combined hypolipidemia	Autosomal recessive	Two affected siblings	ANGPTL3	Co-segregation in family and frameshift mutations at same locus associated with phenotype in previous work	64
Fowler syndrome	Autosomal recessive	Two unrelated cases	FLVCR2	Previous reports of co- segregation in one unrelated family	65
Intractable inflammatory bowel disease; X-linked inhibitor of apoptosis deficiency*	X-linked recessive	One proband	XIAP	Functional assay of PBMCs recapitulating XIAP deficiency and impaired immune reactivity. Bone marrow transplant of affected child improved disease	66
Joubert syndrome 2	Autosomal recessive	Proband and mother	TMEM216	Parallel linkage mapping and candidate re-sequencing in 13 cases from 8 kindreds	67
Mental retardation	Autosomal recessive	Two unaffected parents of five affected siblings	TECR	Co-segregation in family	68
Mental retardation	Sporadic	Ten unrelated cases and their unaffected parents	Several	Previous functional evidence suggests a role for the gene in mental retardation	69
Miller syndrome	Autosomal recessive	Four affected individuals in three kindreds	DHODH	Co-segregation by Sanger sequencing in three separate families	70
Neonatal diabetes mellitus	Autosomal dominant	One proband	ABCC8	Absence of mutation in healthy controls	71
Non-syndromic hearing loss (DFNB82)	Autosomal recessive	Single proband	GPSM2	Co-segregation in family, Not found in 192 controls and 192 unrelated cases	72
Primary Lymphedema	Autosomal dominant	One proband	GJC2	Co-segregation by Sanger sequencing in four additional families	73
Schinzel-Giedion syndrome	Sporadic	Four unrelated cases	SETBP1	Sanger sequencing of 9 unrelated cases and 188 controls	74
Seckel syndrome	Autosomal recessive	Single proband	CEP152	Parallel linkage analysis and candidate region sequencing in a separate family; morphological analysis of CEP152-deficient mitotic cells	75
Spinocerebellar ataxia	Autosomal dominant	Four affected family members	TGM6	Co-segregation of mutations in the same gene in a second family	76
Genome sequencing projects
Charcot-Marie-Tooth Neuropathy	Autosomal recessive	One proband	SH3TC2	Co-segregation with the phenotype by Sanger sequencing in family	77
Metachondromatosis	Autosomal dominant	One proband and partial linkage analysis in family	PTPN11	Co-segregation by Sanger sequencing in a second family	78
Miller syndrome	Autosomal recessive	Two affected offspring and both parents	DHODH, DNAH5, and KIAA0556	Previously published exome sequencing (reference70)	46
Sitosterolemia*	Autosomal recessive	One proband	ABCG5	Presence of sitosterolemia in blood sample after weaning; previous association with sitosterolemia	79

^*Sequence information used to make clinical diagnosis.