A new nonsense mutation in HMX1 in two siblings with oculoauricular syndrome

Figures & data

Table 1. Phenotypic features of OAS patients.

	P1	P2	P3	P4	P5	P6	P7*	P8	P9
Reference(s)	(2,3)	(2,6)	(2,3,6)	(4)	(4)	(5)	(5)	present study	present study
Age at first reported examination	2 months	3 y	6 y	3 days	at birth	40 days	45 days	11 y	9 y
Country of origin	Switzerland	Switzerland	Switzerland	Pakistan	Pakistan	Egypt	Egypt	Pakistan	Pakistan
EYE
Visual acuity	OD 0.05; OS 0.16 (aged 7 y); OD 0.02; OS 0.1 (aged 10 y)	Light perception	0.016 in both eyes, maintained until the age of 65 years	OD 0.125; OS 0.2 (unclear age)	OD 0.16; OS 0.20 (aged 4 y); both eyes 0.025 (aged 9 y); OD light perception; OS 0.016 (aged 14 y)	Decreased	NA	Counting fingers	No light perception
Globe	Microphthalmia	Microphthalmia	Microphthalmia	Microphthalmia	Microphthalmia	Microphthalmia	Microphthalmia	Microphthalmia	Microphthalmia
Axial length	OD 15.5 mm; OS 16.5 mm (unclear age)	NA	NA	OD 13.9 mm; OS 14.9 mm (aged 6 weeks)	OD 16.9 mm; OS 17 mm (unclear age)	OD 19.8 mm; OS 17.9 mm (aged 7 y)	OD 15 mm; OS 16 mm	NA	NA
Cornea	Microcornea with diffuse cornea guttata. Thickness, OD 770 µm; OS 710 µm (aged 7 y)	Sclerocornea	Microcornea	Posterior embryotoxon, localized sclerocornea, microcornea, thickness OD 729 µm; OS 649 µm (aged 6 weeks)	Posterior embryotoxon, sclerocornea, microcornea, progressive corneal opacification (aged 12 y)	Microcornea	Microcornea	Sclerocornea, cornea plana	Severe sclerocornea
Lens	Rapidly progressive congenital cataract	NA	Cataract, microphakia	Dense congenital cataract	Dense congenital cataract	Congenital cataract	Congenital cataract	Congenital cataract	NA
Iris	Posterior synechiae, incomplete coloboma, stromal cyst, corneal adherences	NA	Inferior coloboma	Inferior coloboma	Inferior coloboma, anterior synechiae	Coloboma	Coloboma	Anterior synechiae, inferior coloboma, iris atrophy	NA
Optic disk	Dysplastic, large (Morning Glory-like)	NA	NA	Dysplastic, small	Dysplastic, small	Coloboma, persistent hyaloid artery	Cupping	Pallor	NA
Retina	Macular hypoplasia, peripheral infero-nasal chorioretinal coloboma, progressive rod-cone dystrophy (aged 7 y)	Total retinal detachment (unclear age)	Inferior chorioretinal atrophy, diffuse pigment deposits (aged 65 y)	Chorioretinal coloboma, rod dysfunction (aged 2 y)	Progressive generalized photoreceptor dysfunction (aged 14 y)	Moderate photoreceptor dysfunction (aged 7 y)	NA	Abnormal foveal reflex	NA
Movements	Nystagmus, esotropia (aged 4 y)	Nystagmus	Nystagmus	Nystagmus, exotropia (aged 6 weeks)	Nystagmus (aged 12 y)	Nystagmus	Nystagmus	Nystagmus	Roving
Intraocular pressure	Normal	High	Normal	Normal	Normal	NA	NA	High	NA
EAR
External ear	Lobule aplasia, narrow intertragic incisure, abnormal bridging between the crus of helix and antihelix, narrow external acoustic meatus	Abnormal pinna, lobule aplasia	Abnormal pinna, lobule aplasia	Low-set pinna with crumpled helix, narrow external acoustic meatus, lobule aplasia	Low-set pinna with crumpled helix, narrow external acoustic meatus, lobule aplasia	Large, protruded, and low-set pinna, prominent tragus, antitragus and antihelix, hypoplastic lobule	Large pinna, lobule aplasia	Hypoplastic lobule, abnormal bridging between the crus of helix and antihelix,	Hypoplastic lobule, abnormal bridging between the crus of helix and antihelix,
Hearing	Normal	Normal	Normal	Normal	Normal	Normal	Normal	Normal	Normal

Abbreviations: P = patient; NA = not available; y = years* = genotype not available, sister of P6Visual acuity is expressed in decimals

Figure 1. Family structure, clinical and molecular findings: (a) Pedigree showing segregation of the nonsense mutation (M) p(Arg153Ter) in the HMX1 gene. White and black shapes denote healthy and affected individuals, respectively; squares, males; circles, females; symbols with a diagonal line, deceased; double horizontal lines, consanguineous union. (b) Photographs of eyes and ears of the individuals examined (IV-2 and IV-4). (c) Chromatograms showing segregation of p(Arg153Ter) within the family.

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