Leber Congenital Amaurosis 1

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WHO-ICD-10 version:2010

Diseases of the eye and adnexa

Disorders of choroid and retina

OMIM Number

204000

Mode of Inheritance

Autosomal recessive

Gene Map Locus

17p13.1

Description

Leber's congenital amaurosis (LCA) is a rare inherited retinal dystrophy characterized by vision loss, often from birth. LCA is the most severe form of all inherited retinal dystrophies, accounting for at least 5% of all such cases. It is also one of the main causes of blindness in children. The estimated birth prevalence of LCA is two to three per 100,000 births. There are at least 13 types of Leber congenital amaurosis. These types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities.

Clinical diagnosis is based on clinical history of failure to develop reactions to visual stimuli, roving eye movements or nystagmus, sluggish pupillary responses and a normal, or less frequently an abnormal fundus on dilated fundoscopy. To date, no definitive treatment or cure for LCA exists.

Leber's congenital amaurosis is generally inherited in an autosomal recessive pattern, although some autosomal dominant families have been reported. At least 20 different genes involved in LCA have been identified. LCA type I is caused by mutations in the GUCY2D gene, located on chromosome 17p13.1. This gene is expressed in the photoreceptor cells, where it plays an essential role in normal vision.

Molecular Genetics

All these genes are necessary for normal vision, and play a variety of roles in the development and function of the retina.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
204000.1Saudi ArabiaFemaleNoYes Visual impairment; Congenital nystagmus...NM_001298.3:c.1579C>AHomozygousAutosomal, RecessiveWang et al. 2011
204000.2.1Saudi ArabiaFemaleYesYes Visual loss; Horizontal nystagmus; Ca...NM_015120.4:c.10945G>THomozygousAutosomal, RecessiveWang et al. 2011
204000.2.2Saudi ArabiaMaleYesYes Visual loss; Horizontal nystagmus; C...NM_015120.4:c.10945G>THomozygousAutosomal, RecessiveWang et al. 2011 Brother of 204000.2....
204000.2.3Saudi ArabiaMaleYesYes Visual loss; Horizontal nystagmus; ...NM_015120.4:c.10945G>THomozygousAutosomal, RecessiveWang et al. 2011 Brother of 204000.2....
204000.2.4Saudi ArabiaFemaleYesYes Visual loss; Horizontal nystagmus; ...NM_015120.4:c.10945G>THomozygousAutosomal, RecessiveWang et al. 2011 Sister of 204000.2.1
204000.2.5Saudi ArabiaMaleYesNo Visual loss; Horizontal nystagmus; ...NM_015120.4:c.10945G>THomozygousAutosomal, RecessiveWang et al. 2011 First-cousin of 2040...
204000.2.6Saudi ArabiaFemaleYesNo Visual loss; Horizontal nystagmus; Cat...NM_015120.4:c.10945G>THomozygousAutosomal, RecessiveWang et al. 2011 First-cousin of 2040...
204000.3.1Saudi ArabiaMaleYesYes Visual impairment; Nystagmus; Undetect...NM_000260.4:c.578C>THomozygousAutosomal, RecessiveWang et al. 2011
204000.3.2Saudi ArabiaFemaleYesYes Visual impairment; Nystagmus; Undete...NM_000260.4:c.578C>THomozygousAutosomal, RecessiveWang et al. 2011 Sister of 204000.3.1
204000.3.3Saudi ArabiaMaleYesYes Visual impairment; Nystagmus; Undete...NM_000260.4:c.578C>THomozygousAutosomal, RecessiveWang et al. 2011 Brother of 204000.3....
204000.3.4Saudi ArabiaMaleYesYes Visual impairment; Nystagmus; Unde...NM_000260.4:c.578C>THomozygousAutosomal, RecessiveWang et al. 2011 Relative of 204000.3...
204000.4Saudi ArabiaMaleNoYes Visual impairment; Nystagmus; Undete...NM_001023570.3:c.1479C>AHomozygousAutosomal, RecessiveWang et al. 2011
204000.5Saudi ArabiaMaleYesYes Visual impairment; Nystagmus; Attenuat...NM_001023570.4:c.1130-1G>CHomozygousAutosomal, RecessiveWang et al. 2011 The patient had a gr...
204000.6Saudi ArabiaMaleNoYes Visual impairment; Nystagmus; Attenuat...NM_001023570.4:c.1130-1G>CHomozygousAutosomal, RecessiveWang et al. 2011
204000.7.1JordanFemaleYesYes Intellectual disability; Cataract; Nysta...NM_000180.4:c.2129C>THomozygousAutosomal, RecessiveFroukh. 2017
204000.8Saudi ArabiaUnknownNo Retinal dystrophyNM_000180.4:c.416T>CHomozygousAutosomal, RecessivePatel et al. 2016
204000.9Saudi ArabiaUnknownNo Retinal dystrophyNM_001298.3:c.1573G>A, NM_001298.3:c.955T>CCompound heterozygousAutosomal, RecessivePatel et al. 2016
204000.10Saudi ArabiaFemaleNoYes Visual impairment; NystagmusNM_000180.4:c.1401dupHomozygousAutosomal, RecessiveKhan et al. 2014
204000.11Saudi ArabiaFemaleNoYes Visual impairment; Nystagmus; Eye pokingNM_000180.4:c.1978C>THomozygousAutosomal, RecessiveKhan et al. 2014
204000.12Saudi ArabiaFemaleNoYes Visual impairment; Nystagmus; Eye poking...NM_000180.4:c.1401dupHomozygousAutosomal, RecessiveKhan et al. 2014
204000.13Saudi ArabiaFemaleNoYes Visual impairment; Nystagmus; Eye poking...NM_000180.4:c.1978C>THomozygousAutosomal, RecessiveKhan et al. 2014
204000.14Saudi ArabiaMaleNoYes Visual impairment; Nystagmus; Eye poking...NM_000180.3:c.2285delHomozygousAutosomal, RecessiveKhan et al. 2014
204000.15.1Saudi ArabiaFemaleYesYes Visual impairment; Undetectable electror...NM_000180.4:c.1978C>THomozygousAutosomal, RecessiveLi et al. 2009
204000.15.2Saudi ArabiaMaleYesYes Visual impairmentNM_000180.4:c.1978C>THomozygousAutosomal, RecessiveLi et al. 2009 Brother of 204000.15...
204000.15.3Saudi ArabiaMaleYesYes Visual impairment; Undetectable electror...NM_000180.4:c.1978C>THomozygousAutosomal, RecessiveLi et al. 2009 Brother of 204000.15...
204000.7.GJordanYesYes Blindness; Growth delay; ParalysisNM_000180.4:c.2129C>THomozygousAutosomal, RecessiveFroukh. 2017 6 affected siblings ...
204000.G.1Saudi ArabiaUnknownYes Retinal dystrophyNM_020184.4:c.734C>THomozygousAutosomal, RecessivePatel et al. 2016 Family with unknown ...
204000.G.2Saudi ArabiaUnknownNo Retinal dystrophy; Global developmental ...NM_000180.3:c.2285delHomozygousAutosomal, RecessivePatel et al. 2016 Family with unknown ...
204000.G.3Saudi ArabiaUnknownNo Retinal dystrophyNM_000180.4:c.527T>CHomozygousAutosomal, RecessivePatel et al. 2016 Family with unknown ...
204000.G.4Saudi ArabiaUnknownNo Retinal dystrophyNM_000180.4:c.914delHomozygousAutosomal, RecessivePatel et al. 2016 Family with unknown ...
204000.G.5Saudi ArabiaUnknownYes Cone/cone-rod dystrophyNM_006204.3:c.1613T>CHomozygousAutosomal, RecessivePatel et al. 2016 Family with unknown ...

Other Reports

Algeria

Perrault et al. (1996) conducted genetic analysis for all sibs with Leber congenital amaurosis in two consanguineous Arab-Algerian families and found homozygosity for a T>C transition in exon 8 at nucleotide 1767 of the GUC2D gene.

Saudi Arabia

Soens et al. (2016) reported on a 5-year-old Saudi boy with LCA.  At 6-months of age, the child’s vision was found to be limited to light perception.  He also suffered from nystagmus, the oculo-digit sign and an absent electroretinogram.  Whole exome sequencing found that the patient’s CLUAP1 gene contained a homozygous non-synonymous mutation c.817C>T (c.319C>T in the short isoform), resulting in a p.L273F substitution at a highly conserved residue within the coiled-coil domain (p.L107F in the short isoform).  Functional studies found that the mutation was highly hypomorphic and resulted in a CLUAP1 protein with only 5% of the activity of the wildtype. 

Safieh et al., (2016) described a 6-month old Saudi girl with Leber congenital amaurosis.  She was born to consanguineous parents and was noticed to have rapid synchronous eye movements of both eyes at 40-days of age.  Clinical examination after 18-months showed classical oculodigital sign, moderate bilateral enophthalmos, irregular nystagmus, mild neuro-epithelial atrophy, and mild retinal vascular attenuation.  A novel pathogenic missense mutation in the GUCY2D gene was identified in the patient.  The authors concluded that this mutation expanded the genotypic spectrum of congenital retinal dystrophies in the Saudi population.

Tunisia

Perrault et al. (1996) conducted a genetic analysis for three families from Tunisia with Leber congenital amaurosis. The first family was a Jewish Sephardi family in which affected members were homozygous for a 1-bp deletion (c.460delC) in exon 2 at nucleotide 460 of GUC2D. The second family was of Arab Tunisian origin. Affected members were homozygous for a 1-bp deletion in exon 2 at nucleotide 693 (693delC) of GUC2D. In the third family, a consanguineous Arab Tunisian family, all sibs had homozygosity for a G>T transversion at nucleotide 227 of GUC2D.

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