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Table 4 Results of extended de novo analysisa and C17ORF53 mutation analysis

From: Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours

Gene Genomic position (GRCh37) Variant type Selected transcript and variant effect MAF (Minor allele count/total allele count: 1000 genomes project; EVS; ExAC)b CADD [21] (Phred scaled) PolyPhen-2 [22] (probability) Patient Inheritance
PDE11A chr2:178592832 Synonymous NM_001077196: c.525C>T:p.D175D Not found; Not Found; 0.000016 (2/122254) 11.94 N/A Patient 41 De novo
chr2:178528608 Non-synonymous NM_001077196: c.1300A>G:p.M434V 0.0027 (6/2178); Not found; 0.00032 (39/122690) 18.54 Neutral (0.027) Patient 24 Unknown
Patient 18 Inherited (and present in MZ twin)
chr2:178937010 Non-synonymous NM_016953: c.155G>C:p.R52T 0.0005 (1/2178); 0.0025 (33/13006); 0.0016 (190/118894) 2.494 Neutral (0.016) Patient 5 Unknown
chr2:178936994 Frameshift (1 bp del) NM_016953: c.171del:p.G57fs Not found; Not found; Not found 22.6 N/A Patient 42 Inherited
C17ORF53 c chr17:42226217 Non-synonymous NM_001171251: c.1046T>C:p.I349T Not found; Not found; Not found 5.791 Neutral (0.085) Patient 25 De novo
chr17:42235240 Non-synonymous NM_001171251: c.1810G>A:p.E604K Not found; Not found; 0.000043 (5/117236) 7.093 Neutral (0.494) Patient 5 Unknown
chr17:44162274 3′ UTR NM_001171251: c.*342C > G Not found; Not found; Not found 6.536 N/A Patient 11 Unknown
WDFY4 chr10:50174711 Synonymous NM_020945: c.8577G > T:p.T2859= Not found; Not found; Not found 1.393 N/A Patient 45 De novo
  chr10:50186393 Non-synonymous NM_020945: c.9331C > T:p.R3111W 0.0005 (1/2178); 0.00088 (4/4566); 0.00074 (15/20336) 6.501 Deleterious (0.66) Patient 42 Inherited
FAM199X chrX:103432819 Synonymous NM_207318: c.828C > T:p.S276= Not found; Not found; 0.000024 (3/122866) 15.08 N/A Patient 45 De novo
chrX:103435332 3'UTR NM_207318: c.*876C > G Not found; Not found; Not found 3.885 N/A Patient 18 Inherited (and present in MZ twin)
  1. aAll 16 ROHHAD exomes were searched for candidate variants (as described in methods: novel or rare (MAF < 0.005) exonic, UTR, or splice site (within 2 bp of an exon) variants not within a segmental duplication) within the 13 genes identified as containing de novo variants in one ROHHAD proband
  2. b1000 Genomes Project (http://www.1000genomes.org); EVS = Exome Variant Server (http://evs.gs.washington.edu/EVS/); ExAC = Exome Aggregation Consortium (http://exac.broadinstitute.org)
  3. c Of these four genes, C17ORF53 was selected for mutation analysis in an additional 19 ROHHAD patients. One additional sequence variant was identified through this analysis, and is represented in the bolded row