Clinical relevance of targeted exome sequencing in patients with rare syndromic short stature

Kamil, Gilyazetdinov; Yoon, Ju Young; Yoo, Sukdong; Cheon, Chong Kun

doi:10.1186/s13023-021-01937-8

Orphanet Journal of Rare Diseases

Table 2 Genetic results for patients with short stature

From: Clinical relevance of targeted exome sequencing in patients with rare syndromic short stature

Family	Previous clinical assessment	Previous conventional analysis	Final diagnosis	Gene	Nucleotide/AA change	Inheritance mode	In silico analysis			Initial classification	Re-classification	Novel	References
Family	Previous clinical assessment	Previous conventional analysis	Final diagnosis	Gene	Nucleotide/AA change	Inheritance mode	SIFT	Polyphen-2	Mutation taster	Initial classification	Re-classification	Novel	References
1	NS	PTPN11 SOS1, KRAS, and NRAS	Cleidocranial dysplasia	RUNX2	c.578G>A/p.Arg193Gln	De novo				LPV	PV	No	[45]
2	TS	46,XX	Hajdu–Cheney syndrome	NOTCH2	c.2816C>T/p.Pro939Leu	De novo	Deleterious (0.013)	Benign (0.008)	Disease causing (0.99)	VUS	VUS	Yes
3	USGD	46,XY CMA	Cerebral creatine deficiency syndrome	SLC6A8	c.942_944del/p.Phe315del	Het, mat				LPV	PV	No	[46]
4	NS	PTPN11 SOS1, KRAS, and NRAS	Coffin–Lowry syndrome	RPS6KA3	c.1606G>T/p.Val536Phe	Het, mat	Deleterious (0.00)	Probably damaging (1.00)	Disease causing (0.99)	LPV	PV	Yes
5	USGD	46,XY	Acid-labile subunit deficiency	IGFALS	c.1346T>G/p.Leu449Arg	Com het, pat, mat	Tolerated (0.06)	Probably damaging (0.997)	Disease causing (0.99)	VUS	LPV	Yes
					c.1783C>T/p.Arg595Trp)		Deleterious (0.00)	Probably damaging (1.000)	Disease causing (0.99)	VUS	LPV	Yes
6A	GHS	46,XY, CMA	Sheldon–Hall syndrome	TNNT3	c.47_49del/p.Glu18del	Het, pat				VUS	VUS	Yes
7	USGD	46,XY, CMA	Meckel syndrome (Type 7)	NPHP3	c.73G>T/p.Gly25Cys	Het, pat Het, mat	Deleterious (0.00)	Benign (0.001) (1.00)	Disease causing (0.99)	VUS	LPV	Yes
					c.489T>G/p.His163Gln		Tolerated (0.19)	Probably damaging (0.723)	Disease causing (0.99)	VUS	LPV	Yes
8	CdLS	NIPBL	Coffin–Siris syndrome	ARID1B	c.5547delC/p.Leu1850*	De novo				PV	PV	Yes
9	Achondroplasia	FGFR3	AMDM	NPR2	c.2326C>T/p.Arg776Trp	Het, pat				PV	PV	No	[29, 47]
10	NS	PTPN11 SOS1, KRAS, and NRAS	MR, AD type51	KMT5B	c.2422_2425del/p.Leu808Trpfs*50	De novo				PV	PV	Yes
11	USGD	46,XX, CMA	MR, AR type3	CC2D1A	c.1610C>T/p.Ser537Leu	Homo	Deleterious (0.03)	Probably damaging (0.997)	Disease causing (0.99)	VUS	LPV	Yes
12	CdLS	NIPBL	CdLS type3	SMC3	c.1453_1455delGCT/p.Ala485del	De novo				LPV	PV	Yes
13	CATCH22	CMA	MEIS2-related syndrome	MEIS2	c.998_1000del/p.Arg333del	De novo				PV	PV	No	[48]
14	Skeletal dysplasia	ND	MOPD2	PCNT	c.3716G>A/p.Arg1239His	Compound hetero	Tolerated (0.28)	Probably damaging (0.856)	Tolerated (0.00)	VUS	LPV	No	[49]
					c.7459C>G/p.Leu2487Val		Deleterious (0.00)	Probably damaging (0.997)	Tolerated (0.00)	VUS	LPV	No	[50]
15	USGD	46,XY MLPA	Hajdu–Cheney syndrome	NOTCH2	c.5471G>A/p.Arg1824His	De novo	Deleterious (0.001)	Benign (0.008)	Disease causing (0.99)	VUS	VUS	Yes
16	CATCH22	CMA	MED13L syndrome	MED13L	c.5444C>T/p.Thr1815Met	Het, mat	Tolerated (0.17)	Probably damaging (1.000)	Disease causing (0.99)	VUS	LPV	Yes

AA amino acid, AD autosomal dominant, AMDM acromesomelic dysplasia Maroteaux-type, AR Autosomal recessive, CdLS Cornelia de Lange syndrome, CMA chromosomal microarray, GHS Goldenhar syndrome, hemi hemizygote, het heterozygote, LPV likely pathogenic variant, mat maternal origin, MOPD2 microcephalic osteodysplastic primordial dwarfism type II, MR mental retardation, N/A not available, ND not done, NS Noonan syndrome, pat paternal origin, Pts patients, PV pathogenic variant, Ref references, TS Turner syndrome, USGD unrecognizable syndromic growth disorder, VUS variant of uncertain significance

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ISSN: 1750-1172

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