Leber Congenital Amaurosis (LCA) belongs to the spectrum of early-onset retinal dystrophies. It is a group of monogenic inherited retinal degenerations that show early onset and severe visual dysfunction. Although it is a genetically and phenotypically heterogeneous group of disease it presents in the first few years of life, most often before the age of 1 year and is characterized by wandering nystagmus and reduced vision from birth. Patients may have normal intelligence, but data has demonstrated that as many as 20% develop intellectual disability. The genetic causes of these diseases are due to mutations in genes that play a role in the development and function of the retina and is generally inherited in an autosomal recessive pattern.
The Igenomix Leber Congenital Amaurosis Precision Panel can be used to make an accurate and directed diagnosis as well as a differential diagnosis of blindness ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
The clinical utility of this panel is:
|
GENE |
OMIM DISEASES |
INHERITANCE* |
% GENE COVERAGE (20X) |
HGMD** |
|
|
AIPL1 |
Leber |
AD,AR,X,XR,G |
89 |
82 of 82 |
|
|
CEP290 |
Bardet-Biedl |
AR |
96.47 |
293 of 327 |
|
|
CRB1 |
Leber |
AD,AR,X,G |
99.84 |
365 of 371 |
|
|
CRX |
Cone-Rod |
AD,AR,X,XR,G |
99.91 |
117 of 117 |
|
|
GDF6 |
Klippel- |
AD,AR,MU,D |
98.58 |
19 of 19 |
|
|
GUCY2D |
Choroidal |
AD,AR |
99.98 |
248 of 248 |
|
|
IFT140 |
Retinitis |
AR |
99.97 |
81 of 81 |
|
|
IMPDH1 |
Leber |
AD |
99.98 |
29 of 29 |
|
|
IQCB1 |
Senior- |
AR |
99.98 |
43 of 43 |
|
|
KCNJ13 |
Leber |
AD,AR |
99.64 |
11 of 11 |
|
|
LCA5 |
Leber |
AR |
99.67 |
51 of 52 |
|
|
LRAT |
Leber |
AD,AR,X,XR,G |
100 |
25 of 25 |
|
|
NMNAT1 |
Leber |
AR |
98.94 |
72 of 75 |
|
|
PCYT1A |
Spondylo- |
AR |
99.98 |
22 of 22 |
|
|
PRPH2 |
Choroidal |
AD,AR |
100 |
188 of 188 |
|
|
RD3 |
Leber |
AR |
100 |
13 of 13 |
|
|
RDH12 |
Leber |
AD,AR |
100 |
122 of 122 |
|
|
ROM1 |
Retinitis |
AD,AR,X,XR,G |
100 |
20 of 20 |
|
|
RPE65 |
Leber |
AD,AR |
100 |
231 of 231 |
|
|
RPGRIP1 |
Leber |
AR |
99.33 |
146 of 159 |
|
|
SPATA7 |
Leber Congenital |
AR |
97.02 |
43 of 43 |
|
|
TUBB4B |
Leber |
AD |
100 |
3 of 3 |
|
|
TULP1 |
Leber |
AR |
99.9 |
82 of 82 |
|
|
USP45 |
Leber |
AR |
99.08 |
4 of 5 |
|
* Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial; G: Gonosomal Inheritance; D: Digenic Inheritance
** HGMD: Number of clinically relevant mutations according to HGMD
Tsang, S. H., & Sharma, T. (2018). Leber Congenital Amaurosis. Advances in experimental medicine and biology, 1085, 131–137. https://doi.org/10.1007/978-3-319-95046-4_26
Cideciyan, A. V., & Jacobson, S. G. (2019). Leber Congenital Amaurosis (LCA): Potential for Improvement of Vision. Investigative ophthalmology & visual science, 60(5), 1680–1695. https://doi.org/10.1167/iovs.19-26672
Kumaran, N., Moore, A. T., Weleber, R. G., & Michaelides, M. (2017). Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions. The British journal of ophthalmology, 101(9), 1147–1154. https://doi.org/10.1136/bjophthalmol-2016-309975
Kondkar, A., & Abu-Amero, K. (2019). Leber congenital amaurosis: Current genetic basis, scope for genetic testing and personalized medicine. Experimental Eye Research, 189, 107834. doi: 10.1016/j.exer.2019.107834
Takkar, B., Bansal, P., & Venkatesh, P. (2018). Leber’s Congenital Amaurosis and Gene Therapy. Indian journal of pediatrics, 85(3), 237–242. https://doi.org/10.1007/s12098-017-2394-1
Thompson, J. A., De Roach, J. N., McLaren, T. L., & Lamey, T. M. (2018). A Mini-Review: Leber Congenital Amaurosis: Identification of Disease-Causing Variants and Personalised Therapies. Advances in experimental medicine and biology, 1074, 265–271. https://doi.org/10.1007/978-3-319-75402-4_32
