Table 1 Mendelian diagnoses in this cohort

From: Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders

Presenting phenotype			Genetic testing		Diagnosis
Patient	Grouping	Description	Prior to WES	WES approach	Gene	Pathogenic variant	Inheritance	Disorder	Time to diagnosis
1	Hematological	Moyamoya disease, vasculopathy, renal cysts	CMA, HNF1B & ACTA2 sequencing	Trio	RNF213	NM_001256071.1:c.12416T>G; p.(Leu4139Trp)	AD de novo	Moyamoya disease	3y 2 m
2^a	Hematological	Vitamin B12 deficiency; anemia	Mitochondrial deletions & duplications	Singleton	RPS26	NM_001029.3:c.131_132del; p.(Ile44Serfs*11)	AD de novo	Diamond–Blackfan anemia	4y 2 m
3	ID	Neurodevelopmental disorder, polymicrogyria, epilepsy	CMA	Trio	GRIN2B	NM_000834.4:c.1963A>T; p.(Ile655Phe)	AD de novo	ID disorder/epileptic encephalopathy	4y
4	ID	Microcephaly, moderate developmental delay (DD), cortical visual disturbance	CMA	Trio	FOXG1	NM_005249.4:c.460dup; p.(Glu154Glyfs*301)	AD de novo	Atypical Rett syndrome	2y 6 m
5	ID	ID, hypotonia, posterior cleft palate	CMA	Trio	MED13L	NM_015335.4: c.1708_1709delAG; p.(Ser570Phefs*27)	AD de novo	Syndromic ID	7y 1 m
6	ID	Dysmorphisms, obesity, ID	Subtelomere MLPA, CMA	Trio	SMC1A	NM_006306.2:c.1459G>T; p.(Ala487Ser)	AD de novo	Cornelia de Lange syndrome	11y 6 m
7	ID	ID, movement disorder, epilepsy	AS methylation, karyotype, subtelomere MLPA, CMA, mitochondrial genome & POLG sequencing MECP2 & NKX2-1 sequencing	Singleton	ADCY5	NM_183357.2:c.1252C>T; p.(Arg418Trp)	AD de novo	Familial dyskinesia with facial myokymia	7y 1 m
8^a	ID	Profound DD, macrocephaly, myoclonic seizures	CMA, PTEN sequencing	Trio	PPP2R5D	NM_006245.3:c.592G>A; p.(Glu198Lys)	AD de novo	ID/Overgrowth disorder	7y 2 m
9^a, 10^a	ID	Progressive spastic quadriparesis, moderate ID	CMA, MECP2 duplication	Multiple affected individuals	TANGO2	NM_152906.6:c.420_421delA; p.(Glu142Alafs*2)	AR	Metabolic encephalomyopathic crises and neurodegeneration	13y 4 m 12y 8 m
11	Metabolic	Global DD, static encephalopathy, hyperkinetic movement disorder, frontal bossing, possible mitochondrial disorder	CMA, SURF1, mitochondrial genome & POLG sequencing	Trio	HRAS	NM_005343.2:c.350A>G; p.(Lys117Arg)	AD de novo	Costello syndrome	5y 1 m
12, 13	Neurological	Female limited epilepsy	CMA, PCDH19 & CDKL5 sequencing, EE panel, MECP2 MLPA & sequencing	Multiple affected individuals	IQSEC2	NM_001111125.2: c.2679_2680insA; p.(Asp894Argfs*10)	AD; gonadal mosaicism	X-linked ID/seizures	43y 38y 7 m
14	Skeletal	Craniotubular remodeling disorder; osteosclerosis of skull; low bone mineral density; vitamin deficiencies	CMA	Trio	CLCN7	NM_001287.5:c.1706T>C; p.(Ile569Thr)	AD de novo	Atypical osteopetrosis	2y 6 m
15, 16	Skeletal	Stickler syndrome, recessive	Karyotype, fragile X, COL9A1 sequencing	Multiple affected individuals	PLOD3	NM_001084.4:c.809C>T; p.(Pro270Leu)	AR	Rare connective tissue dysplasia	9y 6 m 13y 4 m
17, 18	Syndromal	Noonan syndrome	Noonan syndrome panel	Multiple affected individuals	RIT1	NM_001256821.1:c.155G>C; p.(Ser52Thr)	AD	Noonan syndrome	19y 1y 8 m
19^a	Visual	Retinitis pigmentosa	None	Singleton	PRPF31	NM_015629.3:c.527+3A>G	AD	Retinitis pigmentosa	35y

Presenting phenotype, successful WES approach, gene diagnosis, inheritance, final clinical diagnosis, and time to WES diagnosis from initial presentation to a specialist with clinical indication for WES.
^aNew diagnoses at 12-month reanalysis.
AD, autosomal dominant; AR, autosomal recessive; AS, Angelman syndrome; CMA, chromosome microarray; EE, epileptic encephalopathy; ID, intellectual disability (all diagnosed had syndromic ID); MLPA, multiplex ligation-dependent probe amplification; WES, whole-exome sequencing.

Back to article page

Table 1 Mendelian diagnoses in this cohort

Search

Quick links