Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations

Silvia De Rubeis; Paige M. Siper; Allison Durkin; Jordana Weissman; François Muratet; Danielle Halpern; Maria del Pilar Trelles; Yitzchak Frank; Reymundo Lozano; A. Ting Wang; J. Lloyd Holder; Catalina Betancur; Joseph D. Buxbaum; Alexander Kolevzon

doi:10.1186/s13229-018-0205-9

Molecular Autism

Table 1 SHANK3 point mutations in 17 individuals described in this study

From: Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations

ID	Coding DNA change^a	Protein change^b	Genomic change (hg19)	Location	Effect	Inheritance	Variant classification [25]
S1^c	c.1527G>A	p.Trp509*	chr22:g.51137146G>A	Exon 12	Nonsense	De novo	Pathogenic
S2	c.2471delC	p.Pro824Argfs*69	chr22:g.51158732delC	Exon 21	Frameshift	De novo	Pathogenic
S3^d	c.2499delG	p.Pro834Argfs*59	chr22:g.51158760delG	Exon 21	Frameshift	De novo	Pathogenic
S4	c.2946_2949delCCGC	p.Arg983Serfs*94	chr22:g.51159207_51159210delCCGC	Exon 21	Frameshift	De novo	Pathogenic
S5	c.3095_3107delTGGGGGCCATCGA	p.Val1032Glyfs*42	chr22:g.51159356_51159368delTGGGGGCCATCGA	Exon 21	Frameshift	De novo	Pathogenic
S6	c.3424_3425delCT	p.Leu1142Valfs*153	chr22:g.51159685_51159686delCT	Exon 21	Frameshift	De novo	Pathogenic
S7	c.3679dupG	p.Ala1227Glyfs*69	chr22:g.51159940dupG	Exon 21	Frameshift	Non-paternal	Pathogenic
S8	c.3679dupG	p.Ala1227Glyfs*69	chr22:g.51159940dupG	Exon 21	Frameshift	De novo	Pathogenic
B1^e	c.3679dupG	p.Ala1227Glyfs*69	chr22:g.51159940dupG	Exon 21	Frameshift	De novo	Pathogenic
S9	c.3764_3776delGGGCCCAGCCCCC	p.Arg1255Leufs*25	chr22:g.51160025_51160037delGGGCCCAGCCCCC	Exon 21	Frameshift	De novo	Pathogenic
B2, B3^e,f	c.4065_4066delTG	p.Val1357Glyfs*4	chr22:g.51160326_51160327delTG	Exon 21	Frameshift	De novo	Pathogenic
S10	c.4229delC	p.Pro1410Hisfs*18	chr22:g.51160490delC	Exon 21	Frameshift	De novo	Pathogenic
S11	c.4577_4578delCC	p.Ala1526Glufs*16	chr22:g.51160838_51160839delCC	Exon 22	Frameshift	De novo	Pathogenic
S12	c.4906_4921dupTCCCCCTCGCCGTCGC	p.Pro1641Leufs*58	chr22:g.51169450_51169465dupTCCCCCTCGCCGTCGC	Exon 22	Frameshift	De novo	Pathogenic
S13^g	c.5008A>T	p.Lys1670*	chr22:g.51169552A>T	Exon 22	Nonsense	Non-maternal	Likely pathogenic
S13^g	c.3872C>T	p.Ser1291Leu	chr22:g.51160133C>T	Exon 21	Missense	Non-maternal	Likely benign
S14	c.5014G>T	p.Asp1672Tyr	chr22:g.51169558G>T	Exon 22	Missense	De novo	Likely pathogenic

^aNM_033517.1
^bNP_277052.1 (Q9BYB0-1)
^cS1 also has a de novo pathogenic 17q12 microduplication [62]. Reported previously [2, 14, 26]
^dReported previously [2, 26]
^eReported previously [24]
^fMonozygotic twins
^gReported previously [26]. This individual has two variants in SHANK3; the missense variant is likely benign and is not shown in Fig. 1a

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