Table 1

Syndromic cataract genes

Gene	Inheritance	Disease	Gene product
PEX10	AR	neonatal adrenoleukodystrophy, Zellweger syndrome	protein of peroxisomal matrix
PEX14	AR	Zellweger syndrome	peroxisomal import machinery
HSPG2	AR	Schwartz-Jampel syndrome type 1/dyssegmental dysplasia	perlecan protein
GALE	AR	galactose epimerase deficiency	UDP-galactose-4-epimerase
POMGNT1	AR	muscular dystrophy-dystroglycanopathy	type 2 transmembrane protein that resides in the Golgi apparatus
ABCD3	AR	Zellweger syndrome 2	member of the superfamily of ATP-binding cassette transporters
COL11A1	AD	Stickler syndrome type 2, Marshall syndrome cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, skeletal dysplasia	one of the 2 alpha chains of type XI collagen
IARS2	AR		Aminoacyl-tRNA synthetase
RAB3GAP2	AR	Martsolf syndrome, Warburg micro syndrome	RAB3 protein regulates exocytosis of neurotransmitters and hormones
GNPAT	AR	rhizomelic chondrodysplasia punctata type 2	enzyme in synthesis of ether phospholipids
PEX13	AR	Zellweger syndrome	peroxisomal membrane protein
RAB3GAP1	AR	Warburg micro syndrome	catalytic subunit of a Rab GTPase activating protein
LRP2	AR	Donnai-Barrow syndrome	low density lipoprotein-related protein 2
CYP27A1	AR	cerebrotendinous xanthomatosis	member of the cytochrome P450 superfamily
KCNJ13	AD	snowflake vitreoretinal degeneration	member of the inwardly rectifying potassium channel family
COL7A1	AR	epidermolysis bullosa dystrophica	alpha chain of type VII collagen
FLNB	AD, AR	Larsen syndrome/spondylocarpotarsal synostosis syndrome	member of the filamin family
CNBP	AD	myotonic dystrophy type 2	a nucleic-acid binding protein with 7 zinc-finger domains
SLC33A1	AR	congenital cataracts, hearing loss, neurodegeneration	required for the formation of O-acetylated (Ac) gangliosides
HMX1	AR	oculoauricular syndrome	transcription factor that belongs to the H6 family of homeobox proteins
CC2D2A	AR	Joubert syndrome 9	play a critical role in cilia formation
SRD5A3	AR	Kahirazi syndrome	steroid 5-alpha reductase family
ETFDH	AR	glutaric acidemia	component of the electron-transfer system in mitochondria
TRAPPC11	AR	muscular dystrophy limb girdle 2S	a subunit of the TRAPP (transport protein particle) tethering complex
ERCC8	AR	Cockayne syndrome type A	a WD repeat protein
VCAN	AD	Wagner syndrome 1	a member of the aggrecan/versican proteoglycan family
SIL1	AR	Marinesco-Sjögren syndrome	resident endoplasmic reticulum N-linked glycoprotein
TFAP2A	AD	branchiooculofacial syndrome	a transcription factor
GCM2	AD	hypoparathyroidism familial isolated	a homolog of the Drosophila glial cells missing gene
NEU1	AR	sialidosis type 2	a lysosomal enzyme that cleaves terminal sialic acid residues
GJA1	AD	oculodentodigital dysplasia	a member of the connexin gene family
PEX7	AR	rhizomelic chondrodysplasia punctata type 1	cytosolic receptor for the set of peroxisomal matrix enzymes
PEX3	AR	Zellweger syndrome	involved in peroxisome biosynthesis and integrity
FAM126A	AR	hypomyelinating leukodystrophy 5	part in the beta-catenin/Lef signaling pathway
PEX1	AR	Zellweger syndrome	a member of the AAA ATPase family
CAV1	AD	partial lipodystrophy, congenital cataracts, neurodegeneration syndrome	main component of the caveolae plasma membranes
AGK	AR	Sengers syndrome	a mitochondrial membrane protein involved in lipid and glycerolipid metabolism
ESCO2	AR	Roberts syndrome	acetyltransferase activity may be required for the establishment of sister chromatid cohesion
EYA1	AD	branchiootorenal syndrome 1	a member of the eyes absent (EYA) family of proteins
PXMP3	AR	Zellweger syndrome	an integral peroxisomal membrane protein required for peroxisome biogenesis
CNGB3	AR	achromatopsia 3	the beta subunit of a cyclic nucleotide-gated ion channel
RECQL4	AR	Rothmund Thompson syndrome	DNA helicase that belongs to the RecQ helicase family
GALT	AR	galatosemia	galactose-1-phosphate uridyl transferase
VLDLR	AR	cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1	low-density lipoprotein receptor
FKTN	AR	muscular dystrophy-dystroglycanopathy	a putative transmembrane protein localized to the cis-Golgi compartment
LMX1B	AD	nail-patella syndrome	a member of LIM-homeodomain family of proteins
POMT1	AR	muscular dystrophy-dystroglycanopathy A1	an O-mannosyltransferase
ERCC6	AR	cerebrooculofacioskeletal syndrome I/Cockayne syndrome type B	a DNA-binding protein that is important in transcription-coupled excision repair
PTEN	AD	Cowden disease	a tumor suppressor
ALDH18A1	AD/AR	cutis laxa AD/cutis laxa AR	a member of the aldehyde dehydrogenase family
OAT	AR	gyrate atrophy of choroid and retina	mitochondrial enzyme ornithine aminotransferase
PTH	AD/AR	familial isolated hypoparathyroidism	a member of the parathyroid family of proteins
LRP5	AR, AD	exudative vitreoretinopathy 4/osteopetrosis, autosomal dominant 1	a transmembrane low-density lipoprotein receptor
DHCR7	AR	Smith-Lemli-Opitz syndrome	an enzyme that removes the C(7–8) double bond in the B ring of sterols
CLPB	AR	3-methylglutaconic aciduria with cataracts, neurologic involvement, neutropenia	member of the ATPases associated with diverse cellular activities (AAA+) superfamily
FZD4	AD	retinopathy of prematurity	a member of the frizzled gene family
MMP1	AR	epidermolysis bullosa dystrophic	a member of the peptidase M10 family of matrix metalloproteinases
CRYAB	AD	myofibrillar myopathy	members of the small heat shock protein (HSP20) family
SC5DL	AR	lathosterolosis	enzyme of cholesterol biosynthesis
JAM3	AR	hemorrhagic destruction of brain, subependymal calcification	immunoglobulin superfamily gene member
TUBA1A	AD	lissencephaly	microtubule constituents of to the tubulin superfamily
PEX5	AR	Zellweger syndrome	protein essential for the assembly of functional peroxisomes
MVK	AR	mevalonic aciduria	peroxisomal enzyme mevalonate kinase
GJB6	AD	Clouston syndrome	one of the connexin proteins
B3GALTL	AR	Peters-plus syndrome	a beta-1,3-glucosyltransferase that transfers glucose to O-linked fucosylglycans on thrombospondin type-1 repeats
ITM2B	AD	cerebral amyloid angiopathy	a transmembrane protein
COL4A1	AD	cerebral small vessel disease	a type IV collagen alpha protein
SEC23A	AR	craniolenticulosutural dysplasia	a member of the SEC23 subfamily of the SEC23/SEC24 family
POMT2	AR	muscular dystrophy-dystroglycanopathy	an O-mannosyltransferase
BUB1B	AR	mosaic variegated aneuploidy syndrome 1	a kinase involved in spindle checkpoint function
FBN1	AD	Weill-Marchesani syndrome	a member of the fibrillin family of proteins
POLG	AD/AR	progressive external ophthalmoplegia with mitochondrial DNA deletions 1	the catalytic subunit of mitochondrial DNA polymerase
GFER	AR?	progressive mitochondrial myopathy, sensorineural hearing loss, developmental delay	structural and functional homolog of the yeast scERV1 gene
NOD2	AD	Blau syndrome	a member of the Nod1/Apaf-1 family
ADAMTS18	AR	Knobloch syndrome	a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family
MAF	AD	Aymé-Gripp syndrome	a DNA-binding, leucine zipper-containing transcription factor
YWHAE	AD	Miller-Dieker lissencephaly syndrome	member of the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins
PEX12	AR	Zellweger syndrome	member of the peroxin-12 family
WNT3	AR	tetraamelia syndrome	secreted signaling proteins implicated in oncogenesis
XYLT2	AR	spondyloocular syndrome	an isoform of xylosyltransferase, which belongs to a family of glycosyltransferases
EPG5	AR	Vici syndrome (immunodeficiency, cleft lip/palate, cataract, hypopigmentation, absent corpus callosum)	a large coiled-coil domain-containing protein that functions in autophagy
CTDP1	AR	congenital cataracts, facial dysmorphism, neuropathy	a protein which interacts with the carboxy-terminus of the RAP74 subunit of transcription initiation factor TFIIF
MAN2B1	AR	alpha-mannosidosis	an enzyme that hydrolyzes terminal, nonreducing alpha-D-mannose residues in alpha-D-mannosides
DMPK	AD	myotonic dystrophy 1	a serine-threonine kinase
FKRP	AR	muscular dystrophy-dystroglycanopathy	a protein which is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan
ABHD12	AR	polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, cataract	an enzyme that catalyzes the hydrolysis of 2-arachidonoyl glycerol
SALL4	AD	Duane-radial ray syndrome	a zinc finger transcription factor thought to play a role in the development of abducens motor neurons
GNAS	AD	pseudohypoparathyroidism type 1A/pseudohypoparathyroidism type 1C/pseudohypoparathyroidism	multiple transcript variants encoding different isoforms
COL18A1	AR	Knobloch syndrome 1	alpha chain of type XVIII collagen
PEX26	AR	Zellweger syndrome	member of the peroxin-26 gene family
NF2	AD	neurofibromatosis type 2	a protein similar to ezrin, radixin, moesin family of proteins
LARGE	AR	muscular dystrophy-dystroglycanopathy	a member of the N-acetylglucosaminyltransferase gene family
MYH9	AD	Fechtner syndrome	a conventional non-muscle myosin
BCOR	XL	microphthalmia syncromic 2	an interacting corepressor of BCL6
PQBP1	XL	Renpenning syndrome	a nuclear polyglutamine-binding protein that is involved with transcription activation
EBP	XL	chondrodysplasia punctata 2	an integral membrane protein of the endoplasmic reticulum
ARSE	XL	chondrodysplasia punctata 1	a member of the sulfatase family
HCCS	XL	linear skin defects with multiple congenital anomalies	an enzyme that covalently links a heme group to the apoprotein of cytochrome c
AIC	XL	Aicardi syndrome	unknown
NHS	XL	Nance-Horan syndrome	a protein containing 4 conserved nuclear localization signals
GLA	XL	Fabry disease	a homodimeric glycoprotein that hydrolyzes the terminal alpha-galactosyl moieties from glycolipids and glycoproteins
COL4A5	XL	Alport syndrome	one of the 6 subunits of type IV collagen
OCRL	XL	Lowe oculocerebrorenal syndrome	an inositol polyphosphate 5-phosphatase
IKBKG	XL	incontinentia pigmenti	regulatory subunit of the inhibitor of kappaB kinase complex

AD, autosomal dominant; AR, autosomal recessive; XL, X linked.

CRYBB2, OCRL

More than 100 genes have been associated with cataracts. 35 genes associated with isolated cataracts and not syndromic.

Next Generation Sequencing / Wes

Some physicians believe when only cataracts, due to high cost, investigation isn’t warranted.

All 3 types of inheritance present, but autosomal dominant is the most frequent. Accounting for 75% of all hereditary cataracts (Book). Can vary among family members and some may not know that they have them

Crystallins are major protein components of the lens and are crucial to maintaining lens transparency. Mutations in crystallin genes represent a large portion of autosomal dominant cataracts. Including CRYAA, CRYBB, CRYAB, CRYGC, and CRYGD. Most cataracts are inherited in autosomal dominant fashion- but some are not