Skip to main content

Table 2 Recessive genes with NAHR-mediated recurrent genomic deletions contributing to more than 20% of the overall disease burden

From: Sequencing individual genomes with recurrent genomic disorder deletions: an approach to characterize genes for autosomal recessive rare disease traits

Gene

AR disease trait

Genomic region cytogenetic interval

NAHR deletion prevalence in adults

NAHR deletion Impact to Recessive Disease (NIRD)

Top 3 allele contribution to diseasea (NAHRdelCNV in bold)

Fraction of NAHRdelCNV allele frequency

Aggregate carrier allele frequency

NPHP1

Nephronophthisis 1, juvenile, MIM# 256100

2q13 NPHP1

5.811x10-3

7.7

98, 3, 2

85

6.82x10-3

ADRA2B

Autosomal recessive mental retardation (from DECIPHER)

2q11.2

7.36x10-5

4.1

95, 10, 10

90

8.18x10-5

ALDOA

Glycogen storage disease XII, MIM# 611881

16p11.2 proximal

5.076x10-4

4.1

95, 10, 10

90

5.64x10-4

CEP19

Morbid obesity and spermatogenic failure, MIM# 615703

3q29

2.136x10-5

4.1

95, 10, 10

90

2.37x10-5

CORO1A

Immunodeficiency 8, MIM# 615401

16p11.2 proximal

5.076x10-4

4.1

95, 10, 10

90

5.64x10-4

COX5A

Mitochondrial complex IV deficiency, nuclear type 20, MIM# 619064

15q24 BPA-BPC

2.374x10-6

4.1

95, 10, 10

90

2.64x10-6

EDC3

Mental retardation, autosomal recessive 50, MIM# 616460

15q24 BPA-BPC

2.374x10-6

4.1

95, 10, 10

90

2.64x10-6

LAT

Immunodeficiency 52, MIM# 617514

16p11.2 distal

1.377x10-4

4.1

95, 10, 10

90

1.53x10-4

MIEF2

Combined oxidative phosphorylation deficiency 49, MIM# 619024

Smith Magenis Syndrome

5.333x10-5

4.1

95, 10, 10

90

5.93x10-5

SLC18A3

Myasthenic syndrome, congenital, 21, presynaptic, MIM# 617239

10q11.21q11.23

1.353x10-4

4.1

95, 10, 10

90

1.50x10-4

PMP22

Dejerine-Sottas disease, MIM# 145900

17p12 HNPP

3.148x10-4

4.2

94, 11, 9

89

3.54x10-4

OTUD7A

Neurodevelopmental disorder (this study)

15q13.3 BP4-BP5

9.97x10-5

5.4

93, 10, 9

74

1.35x10-4

GRAP

Deafness, autosomal recessive 114, MIM# 618456

Smith Magenis Syndrome

5.333x10-5

4.6

91, 41, 7

84

6.38x10-5

RBM8A

Thrombocytopenia-absent radius syndrome, MIM# 274000

1q21.1 TAR

1.78x10-4

9.8

90, 1, 1

90

1.98x10-4

PRODH

Hyperprolinemia, type I, MIM# 239500

22q11.2 LCRA-D

1.417x10-4

5

85, 39, 28

75

1.90x10-4

UQCRC2

Mitochondrial complex III deficiency, nuclear type 5, MIM# 615160

16p12.1

5.84x10-4

5

85, 50, 7

75

7.83x10-4

NDE1

Lissencephaly 4 (with microcephaly), MIM# 614019

16p13.11

3.11x10-4

5.1

84, 54, 15

72

4.30x10-4

PEX11B

Peroxisome biogenesis disorder 14B, MIM# 614920

1q21 TAR

1.78x10-4

4.7

83, 21, 18

72

2.48x10-4

PRRT2

Autosomal recessive mental retardation (from DECIPHER)

16p11.2 proximal

5.076x10-4

5.2

79, 60, 8

65

7.77x10-4

TUFM

Combined oxidative phosphorylation deficiency 4, MIM# 610678

16p11.2 distal

1.377x10-4

3.9

79, 10, 10

65

2.13x10-4

COX10

Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046

17p12 HNPP

3.148x10-4

5.1

77, 48, 25

62

5.05x10-4

POLR3GL

Endosteal Hyperostosis and Oligodontia (from DECIPHER)

1q21 TAR

1.78Ex10-4

4.1

74, 20, 13

59

3.00x10-4

SCARF2

Van den Ende-Gupta syndrome, MIM# 600920

22q11.2 LCRA-D

1.417x10-4

3.8

73, 38, 8

58

2.45x10-4

B9D1

Joubert syndrome 27, MIM# 617120

Smith Magenis Syndrome

5.333x10-5

5.3

72, 74, 12

56

9.47x10-5

MYH11

Megacystis-microcolon-intestinal hypoperistalsis syndrome (from DECIPHER)

16p13.11

3.11x10-4

5

72, 24, 7

57

5.48x10-4

NCAPH

Microcephaly 23, primary, autosomal recessive, MIM# 617985

2q11.2

7.36x10-5

2.9

71, 27, 27

55

1.33x10-4

ANAPC1

Rothmund-Thomson syndrome, type 1, MIM# 618625

2q13

1.258x10-4

3.8

66, 13, 11

50

2.54x10-4

CD19

Immunodeficiency, common variable, 3, MIM# 613493

16p11.2 distal

1.377x10-4

4

65, 38, 28

48

2.86x10-4

HJV

Hemochromatosis, type 2A, MIM# 602390

1q21 TAR

1.78x10-4

5.2

62, 83, 5

45

3.97x104

PIGW

Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025

17q12

6.886x10-4

5.2

61, 64, 35

44

1.56x10-4

IGLL1

Agammaglobulinemia 2, MIM# 613500

22q11.2 LCRD-H

1.187x10-5

5.2

61, 51, 51

43

2.79x10-5

ATPAF2

Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1, MIM# 604273

Smith Magenis Syndrome

5.333x10-5

4.1

58, 78, 12

41

1.29x10-4

CNNM4

Jalili syndrome, MIM# 217080

2q11.2

7.36x10-5

3.2

57, 16, 9

40

1.84x10-4

RBP3

Retinitis pigmentosa 66, MIM# 615233

10q11.21q11.23

1.353x10-4

4.1

58, 30, 9

40

3.42x10-4

SLC25A1

Myasthenic syndrome, congenital, 23, presynaptic, MIM# 618197

22q11.2 LCRA-D

1.417x10-4

4.2

56, 40, 16

38

3.69x10-4

FDFT1

Squalene synthase deficiency, MIM# 618156

8p23.1

9.495x10-6

5.1

55, 53, 53

38

2.52x10-5

GP1BB

Giant platelet disorder, isolated, MIM# 231200

22q11.2 LCRA-D

1.417x10-4

4.6

86, 55, 5

38

3.75x10-4

SGCG

Muscular dystrophy, limb-girdle, autosomal recessive 5, MIM# 253700

13q12.12

2.018x10-4

4.7

53, 25, 16

36

5.62x10-4

CHAT

Myasthenic syndrome, congenital, 6, presynaptic, MIM# 254210

10q11.21q11.23

1.353x10-4

4.1

52, 25, 7

35

3.92x10-4

SNAP29

Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, MIM# 609528

22q11.2 LCRA-D

1.417x10-4

4.3

50, 46, 29

33

4.23x10-4

CDC45

Meier-Gorlin syndrome 7, MIM# 617063

22q11.2_LCRA-D

1.417x10-4

4.2

49, 31, 20

33

4.34x10-4

TBX6

Spondylocostal dysostosis 5, MIM# 122600

16p11.2 proximal

5.076x10-4

5.6

47, 20, 5

47

1.08x10-3

NSMCE3

Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM# 617241

15q11q13 BP3-BP4

3.798x10-5

4.8

91, 46, 4

29

1.29x10-4

NRROS

Seizures, early-onset, with neurodegeneration and brain calcification, MIM# 618875

3q29

2.136x10-5

4.8

93, 44, 2

29

7.48x10-5

TFRC

Immunodeficiency 46, MIM# 616740

3q29

2.136x10-5

1.6

39, 42, 29

24

8.94x10-5

PCYT1A

Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940

3q29

2.136x10-5

1.8

37, 39, 17

22

9.49x10-5

SACS

Spastic ataxia, Charlevoix-Saguenay type, MIM# 270550

13q12.12

2.018x10-4

4.4

36, 14, 13

22

9.09x10-4

OTOA

Deafness, autosomal recessive 22, MIM# 607039

16p12.1

5.84x10-4

4.4

80, 35, 5

21

2.78x10-3

LMAN2L

Mental retardation, autosomal recessive, 52, MIM# 616887

2q11.2

7.36x10-5

3.4

32, 32, 26

19

3.89x10-4

MIPEP

Combined oxidative phosphorylation deficiency 31, MIM# 617228

13q12.12

2.018x10-4

3.9

32, 15, 14

19

1.05x10-3

TXNRD2

Glucocorticoid deficiency 5, MIM# 617825

22q11.2 LCRA-D

1.417x10-4

3.4

49, 37, 31

18

7.86x10-4

ATP2A1

Brody myopathy, MIM# 601003

16p11.2 distal

1.377x10-4

4.1

73, 30, 7

18

7.79x10-4

PI4KA

Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531

22q11.2 LCRA-D

1.417x10-4

4.3

28, 16, 14

16

8.68x10-4

DYNLT2B

Short-rib thoracic dysplasia 17 with or without polydactyly, MIM# 617405

3q29

2.136x10-5

1.1

60, 44, 27

16

1.36x10-4

TANGO2

Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878

22q11.2 LCRA-D

1.417x10-4

2.6

80, 23, 23

13

1.11x10-3

ZNHIT3

PEHO syndrome, MIM# 260565

17q12

6.886x10-5

3.7

96, 22, 2

13

5.47x10-4

ERCC6

Cockayne syndrome, type B, MIM# 133540

10q11.21q11.23

1.353x10-4

3.5

21, 15, 14

12

1.17x10-3

FAN1

Interstitial nephritis, karyomegalic, MIM# 614817

15q13.3 BP4-BP5

9.97x10-5

3.0

23, 21, 20

11

8.94x10-4

ALDH3A2

Sjogren-Larsson syndrome, MIM# 270200

Smith Magenis Syndrome

5.333x10-5

2.7

41, 24, 20

11

4.71x10-4

  1. aThe rows of the table are arranged in a descending order based on the NAHR deletion allele’s contribution to the recessive disease, i.e., the percent of all affected individuals carrying at least one NAHR deletion allele, which are represented as the bold numbers in the column “Top 3 allele contribution to disease.” Note that the numbers from the column “Top 3 allele” are not disjunct events. For example, a patient can be compound heterozygous for the top 1 allele and the 2nd allele, and thus contribute to both numbers. Genes with an NAHR allele contribution to disease lower than 20% are not tabulated here, but can be found in Additional file 1: Table S5