Table 2 Genetic diagnosis obtained by exome sequencing in 200 individuals with idiopathic short stature

Trio 28

ACAN

F

Maternally inherited

chr15(GRCh37):g.89388864C>T

NM_013227.3:c.1180C>T

p.(Arg394*)

Pathogenic (Ib)

Osteochondritis dissecans with short stature

AffOnly 26

ACAN

F

Maternally inherited

chr15(GRCh37):g.89383303del

NM_013227.3:c.515del

p.(Gln172Argfs*59)

Pathogenic (Ib)

Osteochondritis dissecans with short stature

AffOnly 47

ACAN

M

Maternally inherited

chr15(GRCh37):g.89392710C>T

NM_013227.3:c.1774C>T

p.(Gln592*)

Pathogenic (Ib)

Osteochondritis dissecans with short stature

AffOnly 62

ACAN

M

De novo

chr15(GRCh37):g.89401413C>A

NM_013227.3:c.5597C>A

p.(Ser1866*)

Pathogenic (Ia)

Osteochondritis dissecans with short stature

AffOnly 89

ACAN

F

Paternally inherited

chr15(GRCh37):g.89381974T>G

NM_013227.3:c.151T>G

p.(Cys51Gly)

Likely pathogenic (V)

Osteochondritis dissecans with short stature

Trio 11

ANKRD11

M

De novo

chr16(GRCh37):g.89351174_89351180del

NM_001256182.1:c.1770_1776del

p.(Pro591Glyfs*60)

Pathogenic (Ia)

KBG syndrome

Trio 58

CASK

M

Hemizygous

chrX(GRCh37):g.41485893C>T

NM_003688.3:c.979G>A

p.(Glu327Lys)

Likely pathogenic (V)

FG syndrome

Trio 67

CLCN5

M

Hemizygous

chrX(GRCh37):g.49834668C>T

NM_001127899.1:c.298C>T

p.(Arg100Trp)

Likely pathogenic (V)

Hypophosphatemic rickets

Trio 38

COL2A1

M

Paternally inherited

chr12(GRCh37):g.48383569C>A

NM_001844.4:c.1043G>T

p.(Gly348Val)

Likely pathogenic (V)

Stickler syndrome

Trio 62

COL2A1

M

De novo

chr12(GRCh37):g.48370611C>G

NM_001844.4:c.3419G>C

p.(Gly1140Ala)

Pathogenic (IIIb)

Stickler syndrome

AffOnly 4

CUL7

M

Homozygous

chr6(GRCh37):g.43011369C>G

NM_001168370.1:c.3425-1G>C

p.?

Pathogenic (Ib)

3-M syndrome

Trio 27

FGD1

M

Hemizygous

chrX(GRCh37):g.54491974G>C

NM_004463.2:c.1546C>G

p.(Pro516Ala)

Likely pathogenic (V)

Aarskog syndrome

AffOnly 97

FGFR3

M

Maternally inherited

chr4(GRCh37):g.1807363A>G

NM_000142.4:c.1612A>G

p.(Ile538Val)

Pathogenic (IIIb)

Hypochondroplasia

AffOnly 95

FLNB

F

Compound heterozygous

chr3(GRCh37):g.[58149042G>A]/

[58090836C>T]

NM_001164317.1:[c.7276G>A]/

[c.1640C>T]

[p.(Glu2426Lys)]/

[p.(Ala547Val)]

Likely pathogenic (V) / Likely pathogenic (V)

Spondylocarpotarsal synostosis syndrome

Trio 18

GHSR

F

Maternally inherited

chr3(GRCh37):g.172163003G>C

NM_198407.1:c.1049C>G

p.(Thr350Ser)

Likely pathogenic (V)

Isolated partial growth hormone deficiency

AffOnly 77

HDAC6

M

Hemizygous

chrX(GRCh37):g.48681063A>G

NM_006044.2:c.2371A>G

p.(Met791Val)

Likely pathogenic (V)

Chondrodysplasia with platyspondyly

AffOnly 37

IFT140

M

Compound heterozygous

chr16(GRCh37):g.[1573854T>A]/

[1642549C>T]

NM_014714.3:[c.3245A>T]/

[c.410G>A]

[p.(Asp1082Val)]/

[p.(Arg137Gln)]

Likely pathogenic (IV)/ Likely pathogenic (V)

Mainzer–Saldino syndrome

AffOnly 65

IGF1R

M

Maternally inherited

chr15(GRCh37):g.99500379A>G

NM_000875.3:c.3812A>G

p.(Glu1271Gly)

Likely pathogenic (V)

Resistance to insulin-like growth factor 1

AffOnly 84

IHH

M

Maternally inherited

chr2(GRCh37):g.219920354G>A

NM_002181.3:c.811C>T

p.(Leu271Phe)

Likely pathogenic (V)

Brachydactyly, type A1

AffOnly 68

KAT6B

M

De novo

chr10(GRCh37):g.76790228del

NM_012330.3:c.5646del

p.(Asn1883Thrfs*2)

Pathogenic (Ia)

Genitopatellar syndrome

Trio 2

KDM6A

F

De novo

chrX(GRCh37):g.44922973C>T

NM_021140.2:c.1834C>T

p.(Arg612*)

Pathogenic (Ia)

Kabuki syndrome 2

AffOnly 96

KDM6A

F

De novo

chrX(GRCh37):g.44894175G>A

NM_021140.2:c.565-1G>A

p.?

Pathogenic (Ia)

Kabuki syndrome 2

Trio 10

KRAS

M

De novo

chr12(GRCh37):g.25362838T>C

NM_004985.3:c.458A>G

p.(Asp153Gly)

Pathogenic (II)

Noonan syndrome spectrum

Trio 5

MAP2K1

M

De novo

chr15(GRCh37):g.66729175G>C

NM_002755.3:c.383G>C

p.(Gly128Ala)

Pathogenic (IIIa)

Noonan syndrome spectrum

AffOnly 44

MATN3

M

De novo

chr2(GRCh37):g.20194143G>A

NM_002381.4:c.1322C>T

p.(Ser441Phe)

Pathogenic (IIIb)

Multiple epiphyseal dysplasia

AffOnly 50

NF1

F

De novo

chr17(GRCh37):g.29554304A>C

NM_001042492.2:c.2320A>C

p.(Thr774Pro)

Pathogenic (IIIb)

Neurofibromatosis type 1

Trio 28

NPR2

F

Paternally inherited

chr9(GRCh37):g.35799682T>A

NM_003995.3:c.941T>A

p.(Leu314Gln)

Likely pathogenic (V)

Short stature with nonspecific skeletal abnormalities

AffOnly 17

NPR2

F

Paternally inherited

chr9(GRCh37):g.35808587C>T

NM_003995.3:c.2794C>T

p.(Arg932Cys)

Likely pathogenic (V)

Short stature with nonspecific skeletal abnormalities

AffOnly 85

NPR2

F

De novo

chr9(GRCh37):g.35802239C>T

NM_003995.3:c.1669C>T

p.(Arg557Cys)

Pathogenic (IIIb)

Short stature with nonspecific skeletal abnormalities

Trio 77

PDE3A

F

De novo

chr12(GRCh37):g.20769240G>A

NM_000921.4:c.1346G>A

p.(Gly449Asp)

Pathogenic (IIIa)

Hypertension and brachydactyly syndrome

AffOnly 72

PDE4D

F

De novo

chr5(GRCh37):g.58334711G>T

NM_001104631.1:c.896C>A

p.(Ser299Tyr)

Pathogenic (IIIb)

Acrodysostosis 2

AffOnly 74

PTPN11

M

De novo

chr12(GRCh37):g.112915523A>G

NM_002834.3:c.922A>G

p.(Asn308Asp)

Pathogenic (II)

Noonan syndrome spectrum

AffOnly 23

SLC26A2

M

Compound heterozygous

chr5(GRCh37):g.[149361113T>A]/

[149357568T>A]

NM_000112.3:[c.1957T>A]/

[c.353T>A]

[p.(Cys653Ser)]/

[p.(Val118Glu)]

Pathogenic (IIIa)/

Likely pathogenic (IV)

Multiple epiphyseal dysplasia 4

AffOnly 57

TRIM37

M

Compound heterozygous

chr17(GRCh37):g.[57093086dup]/

[57094665_57094666del]

NM_001005207.2:[c.2461dup]/

[c.2377_2378del]

[p.(Ile821Asnfs*6)]/

[p.(Leu793Valfs*2)]

Pathogenic (Ib)/Pathogenic (Ib)

Mulibrey nanism