Table 7.

Lessons Learned: Next-Generation Sequencing of Ten Prenatal Subjects

Subject	Gene(s) of Interest according to Sequencing Results	Interpretation of the Sequencing Results	Clinical Significance	Clinical Outcome
DGAP239	CHD7 (disrupted), LMBRD1 (disrupted)	disruption of an autosomal-dominant gene with a low haploinsufficiency index and associated with CHARGE syndrome (pathogenic) and an autosomal-recessive gene (non-contributory)	pathogenic	CHARGE syndrome
DGAP247	KHDRBS3 (disrupted)	disruption of a single gene without pathogenicity	unknown, likely to be benign	healthy newborn
DGAP248	LRRTM4, RFC3 (disrupted), NBEA	disruption of a gene with a low haploinsufficiency index but no reported pathogenicity; potential dysregulation of an additional gene with a low haploinsufficiency index and reported to be associated with autism-like behaviors in animal models and disrupted in a subject with idiopathic autism45, 46	unknown	termination prior to communication of sequencing results
DGAP258	–	non-genic breakpoints with cryptic paternal inversion not at the karyotypically detected breakpoint	unknown, likely to be benign	healthy newborns
DGAP259	CNTN6 (disrupted), CNTN4, TBC1D5 (disrupted), SATB1, MEF2C, CETN3, CNTNAP2 (disrupted), CUL1, EZH2, SHH, PTPRD (disrupted), L3MBTL4 (disrupted), TCF4, WDR7 (disrupted), NEDD4L	complex rearrangement with potential dysregulation of genes with a low haploinsufficiency index and associated with malformation in the CNS and chromatin organization	pathogenic	termination due to multiple abnormal prenatal findings (bilateral ventriculomegaly and colpocephaly with partial agenesis of the corpus callosum)
DGAP268	CPEB3 (disrupted)	disruption of a single gene without known pathogenicity and a cryptic inversion at non-genic breakpoints	unknown, likely to be benign	healthy newborn
DGAP285	FAM104B (disrupted), MTM1	disruption of a single gene without known pathogenicity; disruption of a TBR with potential dysregulation of a gene associated with X-linked myotubular myopathy, a prenatal-onset fatal disease	unknown, likely to be pathogenic	intrauterine fetal demise (overlapping findings with X-linked myotubular myopathy include decreased fetal movements, hydrocephalus, and stillbirth)
DGAP288	SOX9	non-genic breakpoints with dysregulation of a gene with a low haploinsufficiency index and known to be associated with Pierre Robin sequence	pathogenic	Pierre Robin sequence
DGAP290	HECW2 (disrupted), NUP205 (disrupted)	disruption of two genes without known pathogenicity; non-genic cryptic inversion in one of the breakpoints	unknown, likely to be benign	termination after communication of sequencing results
DGAP295	GFPT1 (disrupted), IGF2	complex rearrangement with potential dysregulation of an imprinted gene associated with Silver-Russell syndrome (pathogenic) and a recessively inherited syndromic gene (noncontributory)	pathogenic	small birth weight and failure to thrive (findings consistent with Silver-Russell syndrome)