Supplementary Table 1 A randomly selected subset of 100 OMIM record pairs cross-referenced by the OMIM curators. To be sure that the 7,000 cross referenced OMIM records in fact were pairs of highly overlapping phenotypes, we manually curated a random subset of 100 record pairs. This investigation shows that 94 of the record pairs had a high degree of phenotypic overlap. 94 out of 100 record pairs are true positives (TP, record pairs cross-referenced because of a high degree of phenotypic overlap). 6 record pairs were false positives (FP, record pairs that were cross-referenced for other reasons than a high degree of phenotypic overlap). Based on this investigation we concluded that the full set of 7,000 pairs could be used as a benchmarking reference for the phenotype similarity score.

In the table we have included a comment stating why there is a phenotypic overlap. If the OMIM text regarding the overlap is very clear, or the overlap is obvious, we have not included a reference to Pubmed, but simply stated OMIM as the reference. If the overlap is not obvious, or the statements in OMIM were ambiguous, we referenced one or more articles describing the phenotypic overlap.

 

Disease (OMIM ID)

Disease (OMIN ID)

Comment

Pubmed ID

Walker-Warburg syndrome Muscular dystrophy, congenital, mental retardation included #236670

FUKUYAMA CONGENITAL MUSCULAR DYSTROPHY

#253800

TP: Two different forms and loci of Muscular dystrophy and mental retardaion

9763366

Muir-Torre syndrome

#158320

Colorectal cancer, hereditary nonpolyposis #120435

TP: Muir-Torre syndrome is a subtype of Colorectal cancer, hereditary nonpolyposis

10544223

Bardet-Biedl syndrome

#209900

Meckel syndrome, type 1

#249000

TP: cystic kidney dysplasia and polydactyly occurs in both syndromes

1488972

Achalasia-Addisonianism-Alacrima syndrome #231550

Addison disease and cerebral sclerosis #300100

TP: “The association of adrenal and neurologic disease in #231550 is similar to that in #300100

OMIM

Knobloch syndrome

#267750

Knobloch syndrome, type II

%608454

TP: Two different forms and loci of Knobloch syndrome

OMIM

Blood group, Froese

#601551

Blood group, Diego system

#110500

TP: Blood group Froese is part of the Diego system. Same molecular basis. “Antigen polymorphism is based on a change in the SLC4A1 gene”

OMIM

11061863

Granulomatous disease, cytochrome b-positive

#233710

Granulomatous disease, cytochrome b-negative #233690

TP: Two different forms and loci of Granulomatous disease

OMIM

Glaucoma 1, open angle, A

#137750

Glaucoma 1, open angle, C

%601682

TP: Two different loci of Glaucoma 1

11436127

Reis-Bucklers Corneal dystrophy #608470

Thiel-Behnke Corneal dystrophy %602082

TP: Two different forms and loci of Corneal dystrophy

7671605

Hypophosphatemic rickets

#300554

Dent disease 1 (Nephrolithiasis, hypercalciuria)

#300009

TP: “Hypophosphatemic rickets is a form of hypercalciuric nephrolithiasis”, “Dent disease complex”

15558518

9452994

Mullerian Aplasia

#158330

Maturity-onset diabetes of the young 1 #125850

TP: Mullerian Aplasia like MODY1 is characterized by frequent complications of diabetic nature including effects on the kidneys. Both conditions caused by mutations in transcription factors influencing e.g. insulin transcription

10484768

Situs invertus viscerum

#270100

Primary ciliary dyskinesia

#242650

TP: Two associated diseases making up Kartagener syndrome #244400

12142464

Hypertension with brachydactyly %112410

Brachydactyly, type E

#113300

TP: Two forms and loci of brachydactyly and hypertension

OMIM

9696728

Primary lateral sclerosis

#606353

Spastic paralysis

#607225

TP: “lateral sclerosis and spastic paralysis are allelic disorders with overlapping phenotypes”

OMIM

Cataract, nonnuclear congenital %601286

Cataract, embryonic nuclear

#604307

TP: Two different forms but associated with same loci

OMIM

8733140

Epidermolysis bullosa dystrophica #132000

Epidermolysis bullosa simplex

#131900

TP: Two different forms and loci of Epidermolysis bullosa

OMIM

7682883

Rett syndrome

#312750

Incontinentia pigmenti

#308300

TP: Some times Rett syndrome co-occurs with incontinentia pigmenti

OMIM

10577905

FG syndrome including partial agenesis of corpus callosum

%305450

Corpus callosum, partial agenesis

#304100

TP: Phenotypically overlapping diseases

OMIM

Medullary cystic kidney disease 1 %174000

Polycystic kidney disease

#173900

TP: Two different form and loci of cystic kidney disease

OMIM

11261687

Nanophthalmos 1

%600165

Nanophthalmos 2

#609549

TP: Two different loci of Nanophthalmos

OMIM

Spondyloepimetaphyseal dysplasia with multiple dislocations %603546

Spondyloepimetaphyseal dysplasia, sponastrime type

%271510

TP: Two different forms and loci of Spondyloepimetaphyseal dysplasia

9678701

Noncompaction of left ventricular myocardium, 1

#604169

Noncompaction of left ventricular myocardium, 2

%609470

TP: Two different loci of Noncompaction of left ventricular myocardium

15173023

Periodic paralysis, potassium-sensitive #170390

Hypokalemic periodic paralysis

#170400

TP: Two different forms and loci of periodic paralysis

12536108

Craniosynostosis, midfacial hypoplasia and foot abnormalies #123150

Apert syndrome

#101200

 

TP: Two different forms and loci of craniosynostosis

11121055

Preeclampsia/eclampsia 3

%609403

Preeclampsia/eclampsia 1

%189800

TP: Two different forms and loci of Preeclampsia/eclampsia

OMIM

Gastric cancer

#137215

Helicobacter pylori infection

#600263

TP: “Helicobacter pylori infection is an established risk factor of gastric cancer, however gastric cancer occurs in only a very small proportion of people infected with the organism”

12115538

Colorectal cancer

#120435

Endometrial cancer

#608089

TP: Endometrial cancer is often co-occurring with colorectal cancer

OMIM

Moyamoya disease 3

%608796

Moyamoya disease 1

%252350

TP: Two different loci of Moyamoya disease

OMIM

Charcot-Marie-Tooth disease 6

#601152

Charcot-Marie-Tooth disease 1B #118200

TP: Two different forms and loci of Charcot-Marie-Tooth disease

OMIM

Premature ovarian failure 1

%311360

Addison disease

%240200

TP: Premature ovarian failure occasionally occur in patients with Addison disease

OMIM

2686250

Pseudohypoaldosteronism, type 1 #264350

Pseudohypoaldosteronism, type II #145260

TP: Two different forms and loci of Pseudohypoaldosteronism

2137831

Specific granule deficiency

#245480

Chediak-Higashi syndrome

#214500

TP: Both disorders characterized by severe defensin deficiency

2841356

Osteosarcoma

#259500

Chondrosarcoma

#215300

TP: Two different forms and loci of sarcoma

OMIM

Ichthyosis, lamellar 1

#242300

Ichthyosis, lamellar 2

#601277

TP: Two different forms and loci of Ichthyosis

OMIM

von Hippel-Lindau syndrome

#193300

Pheochromocytoma

#171300

TP: “Pheochromocytomas most commonly occur as part of several syndromes including von Hippel-Lindau syndrome”

OMIM

Arthrogryposis, type 5

%108145

Arthrogryposis, type 2B

#601680

TP: Two different forms and loci of Arthrogryposis

OMIM

8923935

Dementia with spastic ataxia

#176500

Creutzfeldt-Jakob disease

#123400

TP: Overlapping phenotypes. Dementia and another form of ataxia is part of the clinical synopsis for Creutzfeldt-Jakob disease.

OMIM

Coffin-Siris syndrome

%135900

Biotinidase deficiency

#253260

TP: Case report identifying an association between the two diseases

2373113

Systemic lupus erythematosus 7 %610065

Systemic lupus erythematosus

#152700

TP: Different loci of Systemic lupus erythematosus

OMIM

16642431

Pancreatic carcinoma

#260350

Peutz-Jeghers syndrome

#175200

TP: Increased risk of pancreatic cancer in patients with Peutz-Jeghers syndrome

OMIM

Pseudovitamin D3 deficiency Rickets due to 25-hydroxylase deficiency #600081

Vitamin D-dependent Rickets type 1

TP: Two different forms and loci of Vitamin D-dependent Rickets

OMIM

Ceroid lipofuscinosis, neuronal 6 #601780

Ceroid lipofuscinosis, neuronal 3 #204200

TP: Two different forms and loci of Ceroid lipofuscinosis, neuronal

OMIM

9097964

Thyrotoxic periodic paralysis

#188580

Hashimoto thyroiditis

%140300

TP: Two phenotypically overlapping diseases

OMIM 3839536

Pilomatrixoma

#132600

Rubinstein-Taybi syndrome

#180849

TP: “Occurrence of pilomatrixomas in Rubinstein-Taybi syndrome”

9557902

Myopathy, myofibrillar, desmin-related #601419

Myopathy, myofibrillar, myotilin-related #609200

TP: Two different forms and loci of Myopathy

OMIM

Hyperthyroidism

#609152

Hypothyroidism

#275200

FP: Both conditions can be caused by mutations in TSHR, but clinical phenotypes have little overlap

OMIM

Charcot-Marie-Tooth disease dominant intermediate D

#607791

Charcot-Marie-Tooth disease dominant intermediate A

%606483

TP: Two different forms and loci of Charcot-Marie-Tooth disease

OMIM

Glioma of brain

#137800

Cowden disease

#158350

FP: From abstract, “the patient did not show any of the clinical signs of Cowden disease”.

12085208

Congenital alopecia

#601705

Omenn syndrome

#603554

TP: Two sisters with congenital alopecia #601705. Alopecia is highly frequent in Omenn syndrome

11795679

Hypomagnesemia 2

#154020

Hypomagnesemia with secondary hypocalcemia

#602014

TP: Two different forms and loci of Hypomagnesemia

9915957

Craniosynostosis, Type 1

%123100

Greig cephalopolysyndactyly syndrome

#175700

TP: Craniosynostosis is part of the clinical synopsis of Greig cephalopolysyndactyly, although craniosynostosis is described three times in the literature as NOT being part of Greig cephalopolysyndactyly 7521123, 8188211, 223435

OMIM

Chondrodysplasia punctata 2

#302960

Epilepsy, with mental retardation.

%300088

TP: Several reports where Chondrodysplasia punctata and epilepsy/mental retardations are connected

15658616

Pancreatic insufficiency and bone marrow dysfunction

#260400

Asphyxiating thoracic dystrophy

%208500

TP: Skeletal abnormalities part of both diseases

OMIM

999326

Muscular dystrophy, Type 1 F

%608423

Muscular dystrophy, Type 1 A

#159000

TP: Two different forms and loci of Muscular dystrophy

11222786

Attention deficit-hyperactivity disorder 2 %608904

Attention deficit-hyperactivity disorder 1 %608903

TP: Two different loci of Attention deficit-hyperactivity disorder

15297934

Albright hereditary osteodystrophy #103580

Major affective disorder

%309200

FP: The link of the diseases are due to their mode of inheritance

6770678

Major affective disorder 1

%125480

Major affective disorder 2

%309200

TP: Two different loci of Major affective disorder

OMIM

11149935

Malignant hyperthermia 1

#145600

Malignant hyperthermia 4

%600467

TP: Two different loci of Malignant hyperthermia

OMIM

12522565

Cataract, anterior polar 2

%601202

Cataract, anterior polar 1

%115650

TP: Two different loci of anterior polar cataract

OMIM

8852669

Prostate cancer aggressiveness QTL %607592

Prostate cancer

#176807

TP: Two different loci of Prostate cancer

10825281

Parkinson disease 9

%606693

Pallidopyramidal syndrome

%260300

TP: “clinical features similar to those of idiopathic Parkinson disease and Pallidopyramidal syndrome”

8085432

Hypertension

#145500

Pseudohypoaldosteronism 1

#264350

FP: Opposite clinical phenotypes. However, both conditions are caused by changed renal tubular Na+ absorption (hypertension: increased. PHA-1: decreased)

15931322

Spinocerebellar ataxia 2

#183090

Spinocerebellar ataxia 6

#183086

TP: Two different forms and loci of Spinocerebellar ataxia

16613893

Amyloidosis corneal

#204870

Amyloidosis V

#105120

TP: Two forms and loci of amyloidosis

OMIM

10729296

Globoid cell leukodystrophy

#245200

Metachromatic leukodystrophy

#250100

TP: Two forms and loci of leukodystrophy

16763970

Granunomatous disease, x-linked #306400

Duchenne muscular dystrophy

#310200

FP: Case study. One patient had 3 x-linked disorders incl. Granunomatous disease and Duchenne muscular dystrophy. Deletion of part of Xp21

4039107

Lymphedema-Distichiasis syndrome #153400

Lymphedema, hereditary II

#153200

TP: “Allelic disorders with overlapping phenotypes include Lymphedema type II”

10086462

Celiac disease susceptibility to 1 #212750

Celiac disease susceptibility to 3 #609755

TP: Two different loci of Celiac disease

16820991

GM2-gangliosidosis type II

#268800

Gaucher disease type 1

#230800

TP: “Gaucher disease, a related disorder that involves glycosphingolipid storage in peripheral tissues but not in the central nervous system”

OMIM

16854371

Inflammatory bowel disease 2

%601458

Inflammatory bowel disease 1

#266600

TP: Two different loci of Inflammatory bowel disease

16873002

Episodic ataxia, type 1

#160120

Episodic ataxia, type 2

#108500

TP: Two different forms and loci of Episodic ataxia

9390841

Brachydactyly, type A1

#112500

Brachydactyly, type A1, B

%607004

TP: Two different loci of Brachydactyly, type A1

11897820

Usher syndrome, type IIB

%276905

Usher syndrome, type IIA

#276901

TP: Two different forms and loci of Usher syndrome type II

11950859

Craniofacial-deafness-hand syndrome #122880

Waardenburg syndrome, type 1 #193500

TP: Several overlapping clinical traits between the diseases.

14556253

Major depressive disorder

#608516

Major depressive disorder 2

%608691

TP: Two different loci of Major depressive disorder

OMIM

8966556

Waardenburg syndrome type IIA #193510

Waardenburg syndrome type IIB %600193

TP: Two different forms and loci of Waardenburg syndrome

331943

Orofacial cleft 5

#608874

Orofacial cleft 1

%119530

TP: Two different loci of Orofacial cleft

16282779

Thanatophoric dysplasia

#187600

Asphyxiating thoracic dystrophy %208500

TP: Many phenotypically overlapping features

OMIM

Night Blindness, congenital type 1 #310500

Aland Island eye disease

%300600

TP: “congenital stationary night blindness and Aland Island eye disease could be considered as a single entity”

7612552

Charcot-Marie-Tooth disease type 2A1 #118210

Charcot-Marie-Tooth disease type 2A2 #609260

TP: Two different forms and loci of Charcot-Marie-Tooth disease

OMIM

Myopia 12

%609995

Myopia 2

%160700

TP: Two different forms and loci of Myopia

OMIM

Migraine, familial typical, 2

%300125

Migraine with or without aura, 1

%157300

TP: Two different forms and loci of Migraine

OMIM

Dyslexia, susceptibility to 1

#127700

Dyslexia, susceptibility to 8

%608995

TP: Two different forms and loci of Dyslexia

OMIM

Chordoma

%215400

Tuberous sclerosis complex

#191100

TP: “identified 3 reports of chordomas found in patients with tuberous sclerosis complex”

15236319

Granulomatous disease, cronic, x-linked #306400

Granulomatous disease, cronic, autosomal recessive #233710

TP: Two forms and loci of Granulomatous disease

OMIM

Ulcerative colitis

#191390

Inflammatory bowel disease 2

%601458

TP: Two different forms and loci of inflammatory bowel disease

OMIM

Velocardiofacial syndrome

#192430

Asperger syndrome 1

%608638

TP: VCF is caused by mutation in TBX1. There is evidence for that “TXB1 haploinsufficiens may cause psychiatric disorders like ASP-1, although based only on casuistic reports”

16684884

Hair color 3

%601800

Eye color 3

%227220

TP: Association study shows the two traits are significantly inherited together

8875191

Alopecia-mental retardation

%203650

Hair-brain syndrome

#234050

TP: Overlapping phenotypes; mental retardation and abnormal hair growth.

OMIM

Epilepsy, idiopathic generalized #600669

Epilepsy, grand mal seizures on awakening #607628

TP: Two different forms and loci of epilepsy

 

OMIM

Hereditary myopathy with early respiratory failure #603689

Duchenne muscular dystrophy

#310200

TP: Two different forms and loci of myopathy

OMIM

Wolfram syndrome 1

#222300

Wolfram syndrome 2

%604928

TP: Two different loci of Wolfram syndrome

10739754

Pancreatic carcinoma

#260350

Melanoma, cutaneous malignant %155600

TP: “Several familial cancer syndromes increase the risk of pancreatic cancer…”

OMIM

Piebald trait

#172800

Fanconi anemia

#227650

TP: “White forelock and patches leukoderma occur also in Fanconi anemia”

OMIM

Glaucoma 1, open angle, A

#137750

Glaucoma 1, open angle, J

%608695

TP: Two different loci of Glaucoma 1, open angle

15108121

Oral-facial-digital syndrome IX

%258865

Oral-facial-digital syndrome  II

%252100

TP: Two different forms and loci of Oral-facial-digital syndrome

8074150

Hydranencephaly, fowler type

%225790

Fetal akinesia deformation sequence (FADS) %208150

TP: Case study, both diseases included

11857548

Vitamin D-dependent rickets type II %600785

Vitamin D-dependent rickets type I #264700

TP: Two different forms and loci of Vitamin D-dependent rickets

OMIM

Cholestasis, progressive familial intrahepatic 2 #601847

Cholestasis, progressive familial intrahepatic 1 #211600

TP: Two different forms and loci of Cholestasis, progressive familial intrahepatic

OMIM

Vohwinkel syndrome

#124500

Vohwinkel syndrome with ichthyosis #604117

TP: Two different forms and loci of Vohwinkel syndrome

OMIM

 

 

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