Ismail K Jalili


Retinal ciliopathies: List of cone-rod ciliopathies and mutations in Jalili Syndrome.

Jalili IK. November 2010. Revised November 2011.

Cone-rod dystrophies (CRD) are part of a wide spectrum of progressive photoreceptor disorders becoming known collectively as retinal ciliopathies. Photoreceptor dystrophies are categorised on the basis of the photoreceptor cells primarily involved  in the disease process as depicted by electrophysiology. Within this spectrum, three main groups are recognised; cone-rod, rod-cone and mixed receptors dystrophies. In the former (CRD), cones are the cells predominately involved in the disease process, at least initially. Rod-cone dystrophies (RCD) form the other end of this spectrum whereby rods are the primarily affected cells, the term retinitis pigmentosa (RP) is now commonly reserved for this latter group. In between lie rarer and more complex clinical entities, mixed receptors dystrophies, in which both photoreceptor types are severely compromised from onset. The commonest entity in the latter is Leber congenital amaurosis (LCA) in which night blindness, as initially described by Leber, is an important feature. More recently less recognised conditions with photophobia from different genetic mutations have been included under the term LCA, although the term congenital amaurosis of the cone-rod (CACR) was suggested as an alternative for this subgroup to identify them as separate clinical entities Retinal ciliopathies can occur as isolated retinal conditions or in combination with other ciliopathies which encompass ectodermal, cerebrorenal and metabolic disorders and are caused by a wide array of genetic mutations, (Jalili, 2010)

Retinal ciliopathies can occur as isolated retinal conditions or in combination with other ciliopathies which encompass ectodermal, cerebrorenal and metabolic disorders and are caused by a wide array of genetic mutations.1-19

Cone-Rod Ciliopathies:

A) Ectodermal Disorders

Amelogenesis imperfecta

Jalili syndrome (OMIM 217080) 20, 21

CNNM4: 2q115, 6

Retinal phenotype A
Gaza A c.599→A; p.Ser200yr 5

Kosovar 1  c.1312dupC; p.Leu438ProfsX9 5 22

Kosovar 2 c.1312 dupC; p.Leu438PfsX9 5

Kosovar 3 c.1312dupC / p.Leu438ProfsX9 23

Lebanese c.707G→A; p.R236Q 6

Unknown c.971T→C; p.L324P 6

Retinal Phenotype B

Gaza B c.1813C→T; p.Arg605X 5

Scottish c.971T→C; p.Leu324Pro /

c.1690C→T; p.Gln564X 5

Turkish c.586T→C; p.Ser196Pro 5

Retinal phenotype unspecified

Iranian  c.1-?_1403+?del 5

Guatemalan c.2149C→T; p.Gln717X) /

c.62_145del; p.Leu21HisfsX185 5

Hypertrichosis with trichomegaly (OMIM 204110) 1

Cone-rod congenital amaurosis 1

Hypotrichosis (OMIM 601553)

Hereditary Juvenile macular degeneration (HJMD)
CDH3 (16q22.1) 7
Group1: Single nucleotide deletion (981delG) encoding P-cadherin

Group 2: Missense mutation (R503H) 9

Alopecia of scalp and eyelashes 10

Aplasia cutis congenital with high myopia (OMIM 600360) 11 

B) Dysmorphic Syndromes

Spondylometaphyseal dysplasia 2, 13,14

cleft lip 14

C) Metabolic Dysfunctions

Thiamine-responsive megaloblastic anaemia (TRMA, Rogers syndrome, (OMIM 249270) 15

SLC19A2 loc 1q23.3

D) Cerebro-Renal Disorders

Bardet Biedl syndrome and Variants (OMIM 209900) 16, 24, 25

BBS1 (BBS2L2): 11q13.1

BBS2 (BBS, MGC20703): 16q21 (c.565C>T;p.ArgR189Stop)

ARLS6 (BSS3): 3q11.2

BBS4: 15q22.3-q23

BBS5: 2q31.1

MKKS (BBS6): 20p12

BBS7 (BBS2L1): 4q27

TTC8 (BSS8): 14q31.3

BBS9 (B1, C18, D1, MGC118917): 7p14

BBS10: 10 D1

TRIM32 (BBS11): 9q33.1

BSS12 (C4orf24): 4q27

MKS1 (BBS13): 17q22

CEP290 (BBS14): 12q21.32

TMEM67 (HBTS6, MKS3): 8q22.1

Biemond syndrome (plus iris coloboma)

Alström syndrome (OMIM 203800) 17



Spinocerebellar ataxia type 7 (OMIM 164500) 18, 19 

ATXN7 (ADCAII, OPCA3, SCA7): 3p21.1-p12


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Ismail K Jalili 2000-2016