Table 1 Genotype–phenotype data of patients diagnosed with DMS

1.1 Osteogenesis imperfecta

 1.1.1

3/F

Frequent falls, multiple fractures, blue sclera

No

 + 

Pathogenic

COL1A1 c.3008delC p.Pro1003leufsTer105

Het

Osteogenesis imperfecta I

 1.1.2

29/M

Cannot walk, recurrent fractures

No

 − 

Likely pathogenic COL1A2 c.1045G > T

p.Gly349Cys

Het

Osteogenesis imperfecta III

 1.1.3

12/M

Recurrent fractures, osteogenesis imperfecta and blue sclera

No

 + 

Likely pathogenic COL1A2 c.838G > Ap.Gly280Ser

Het

Osteogenesis imperfecta I

 1.1.4

16 y/M

Developmental delay, post fall- multiple cranial bone fractures, rt facial paralysis also, blue sclerae

No

 − 

Pathogenic

COL1A1 c.1588G > A

p.Gly530Ser

Het

Osteogenesis imperfecta II

 1.1.5

12 y/M

Recurrent fractures, dentinogenesis imperfecta, slurred speech, dysmorphism, blue sclera, mild scoliosis, high arched palate

No

 − 

VUS

COL1A1 c.1861 C > A

p.Pro621Thr

Hom

Osteogenesis imperfecta I

 1.1.6

5/M

Frequent falls, Multiple fractures, Bluish grey sclera

No

 + 

rs2075555

Polymorphism COL1A2 c.804 + 80A > C

Hom

Osteogenesis imperfecta I

 1.1.7

32/M

Scoliosis, multiple fractures in childhood, paraplegic

Yes

 + 

VUS

SERPINF1 c.415G > C p.A139P

Hom

Osteogenesis imperfecta VI

 1.1.8

5/M

Recurrent fractures and blue sclera

No

 − 

NA

NA

Negative

1.2 Osteopetrosis

 1.2.1

25/M

Frequent falls since childhood with multiple limb fractures

Yes

 + 

Pathogenic CLCN7 c.856CC/T p.Arg286Trp

Het

Osteopetrosis 2

 1.2.2

2/M

Hypotonia, macrocephaly, both humerus bones fractured in neonatal period

No

-

VUS

LRP c.713C > T

p.Thr238Met

Het

Osteopetrosis 1

1.3 Split-hand/foot malformation

 1.3.1

7 year/F

Ectrodactyly

Yes

 + 

Pathogenic WNT10B c.499_500delCT

(p.Leu167ValfsTer33)

Hom

Split-hand/foot

Malformation-6

1.4 Skeletal dysplasia with in utero presentation

 1.4.1

20 weeks/M

POC

Polyhydramnios and musculoskeletal dysplasia

No

 + 

VUS

MTM1 c.413C > T p.Thr138Met

X-Hemi

Myotubular myopathy

 1.4.2

20 weeks/M

POC

Skeletal dysplasia in utero

Yes

 + 

Novel

Pathogenic CUL7 c.867_877del p.Gln289HisfsTer2

Hom

3 M syndrome 1

 1.4.3

2 days/F

Microcephaly, small sized cerebellum, Dandy walker malformation oligohydramnios, hypoplasia,

Yes

 + 

VUS POMT1 c.123-4C > T

Novel VUS POMT1

C.280 + 7_280 + 9AG

Compound het

Walker–Warburg syndrome

 1.4.4

Couple

Pregnancy with increased nuchal translucency, absent nasal bone, pleural effusion, small cardiac size with small left ventricle, bilateral talipes

Yes

 + 

Novel Pathogenic

CEP290c.6134C > T, p.Ser2045Leu

VUS CEP290 c.7394_7395del, p.Glu2465ValfsTer2

Het

Joubert syndrome 5

 1.4.5

Couple

Microcephaly in fetus

Yes

 − 

Likely pathogenic RBBP8 c.604 + 1G > T

Het

Seckel syndrome 2

 1.4.6

Couple

Child with skeletal dysplasia in utero with respiratory insufficiency at birth

Yes

 − 

VUS

COL11A2 c.3133G > G/T p.Gly1045Ter

Het

Fibrochondrogenesis 2

1.5 Short stature

 1.5.1

31 year/F

Short stature, renal rickets

No

 + 

Pathogenic PHEX c.1601C > T p.Pro534Leu

Het

Hypophosphatemic rickets

 1.5.2

12 y/F

Atrophy of brain stem, pons and cerebellum, short stature

Yes

 + 

Pathogenic ERC66 c.4063-1G > C

(3’ Splice site)

Hom

Cockayne syndrome B,

Cerebrooculofacioskeletal

Syndrome 1

 1.5.3

4 year/M

Oligohydramnios, short stature, poor

suck, global development delay, microcephaly,

No

 − 

VUS CUL4B c.65G > A

p.Gly22Asp

Hemi

Cabezas type of X-linked syndromic

mental retardation

 1.5.4

5 year/M

Developmental delay, dysmorphism short stature, toe walking

No

 − 

VUS AHDC1 c.Gly2618Thr

Het

Xia–Gibbs syndrome

1.6 Joint stiffness and pain

 1.6.1

21/M

Bone pain, Erlenmeyer flask deformity of distal tibia and fibula, thrombocytopenia, renal parenchymal changes, renal cortical cyst, elevated levels of alkaline phosphatase and atrial septal defect

Yes

 + 

Novel Pathogenic SLCO2A1 c.325delG

p.Ala109LeufsTer64

Hom Het

Primary hypertrophic osteoarthropathy, autosomal recessive 2

 1.6.2

16 y/M

Joint restrictions, delayed speech, seizures, breathing problems

No

 − 

Pathogenic CCN6: c.156C > A

p.Cys52Ter

Hom

Pseudorheumatoid dysplasia

 1.6.3

8 y/F

Difficulty walking, stiffness in left knee, pigeon chest genu valgum, avascular necrosis in right hip

No

 − 

Pathogenic

COL9A1

c.2755C > T

p.Pro919Ser

Het

Multiple

Epiphyseal

Dysplasia

 1.6.4

8 m/M

Joint swellings and hyper pigmentation

Yes

 − 

Novel Likely pathogenic ANTXR2 c.54_60dupGCTG

TGG

(p.Leu21Alafs*26)

Hom

Hyaline fibromatosis

Syndrome

 1.6.5

30/F

Café au lait spots, scoliosis, back pain

No

 + 

Pathogenic

NF1 c.4968_4969delAG (p.Asp1657LeufsTer4)

Het

Neurofibromatosis 1