Characterization of<i>CDH3</i>-Related Congenital Hypotrichosis With Juvenile Macular Dystrophy

Hull, Sarah; Arno, Gavin; Robson, Anthony G.; Broadgate, Suzanne; Plagnol, Vincent; McKibbin, Martin; Halford, Stephanie; Michaelides, Michel; Holder, Graham E.; Moore, Anthony T.; Khan, Kamron; Webster, Andrew R.

doi:10.1001/jamaophthalmol.2016.2089

Cited by 20 publications

(25 citation statements)

References 36 publications

(64 reference statements)

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“…1). This is an unusual and infrequently encountered pattern of degeneration, but one that is shared with other monogenic retinopathies, where the underlying gene regulates cell–cell adhesion ( ADAM9 , CDH3 ) [39, 40]. Fourth, retinal thickening and loss of lamination may be evident, another phenotypic clue suggestive of CRB1 -associated retinopathy [41].…”

Section: Discussionmentioning

confidence: 99%

A clinical and molecular characterisation of CRB1-associated maculopathy

et al. 2018

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To date, over 150 disease-associated variants in CRB1 have been described, resulting in a range of retinal disease phenotypes including Leber congenital amaurosis and retinitis pigmentosa. Despite this, no genotype–phenotype correlations are currently recognised. We performed a retrospective review of electronic patient records to identify patients with macular dystrophy due to bi-allelic variants in CRB1. In total, seven unrelated individuals were identified. The median age at presentation was 21 years, with a median acuity of 0.55 decimalised Snellen units (IQR = 0.43). The follow-up period ranged from 0 to 19 years (median = 2.0 years), with a median final decimalised Snellen acuity of 0.65 (IQR = 0.70). Fundoscopy revealed only a subtly altered foveal reflex, which evolved into a bull’s-eye pattern of outer retinal atrophy. Optical coherence tomography identified structural changes—intraretinal cysts in the early stages of disease, and later outer retinal atrophy. Genetic testing revealed that one rare allele (c.498_506del, p.(Ile167_Gly169del)) was present in all patients, with one patient being homozygous for the variant and six being heterozygous. In trans with this, one variant recurred twice (p.(Cys896Ter)), while the four remaining alleles were each observed once (p.(Pro1381Thr), p.(Ser478ProfsTer24), p.(Cys195Phe) and p.(Arg764Cys)). These findings show that the rare CRB1 variant, c.498_506del, is strongly associated with localised retinal dysfunction. The clinical findings are much milder than those observed with bi-allelic, loss-of-function variants in CRB1, suggesting this in-frame deletion acts as a hypomorphic allele. This is the most prevalent disease-causing CRB1 variant identified in the non-Asian population to date.

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Section: Discussionmentioning

confidence: 99%

A clinical and molecular characterisation of CRB1-associated maculopathy

et al. 2018

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“…Several findings of this case report are unique. This is the first instance of two previously undescribed mutations: CDH3 c.1660A > C and DNAH5 c.6688-1G>T 8 , 25 . Additionally, this the first report of OCT angiography in a patient with HJMD.…”

Section: Resultsmentioning

confidence: 65%

“…Several findings of this case report are unique. This is the first instance of two previously undescribed mutations: CDH3 c.1660A > C and DNAH5 c.6688-1G>T. 8 , 25 Additionally, this the first report of OCT angiography in a patient with HJMD. Our patient's vision loss in conjunction with progressive sinopulmonary disease led to the diagnosis of two separate diseases, one with known retinal degeneration and the other without any prior reported association with vision loss.…”

Section: Discussionmentioning

confidence: 72%

“…4 ). 8 This is the first report of HJMD to illustrate OCT angiography findings. Although no normative database of OCT angiography exists for pediatric patients, there appears to be patchy flow voids of the choriocapillaris in both eyes ( Fig.…”

Section: Discussionmentioning

confidence: 78%

“…Additionally, this specific patient had no family history of HJMD or PCD and presented at a relatively early age of 11 years old with below average visual acuity impairment compared to other reported cases. 6 HJMD is known to cause a longitudinal deterioration of cone and rod mediated function, 5 , 6 , 8 therefore recognizing the symptoms, visual impairment, physical examination, and photographic and electrophysiological findings is crucial in counseling the patient, the family, and fellow clinicians.…”

Section: Discussionmentioning

confidence: 99%

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A unique case of vision loss in a patient with hypotrichosis and juvenile macular dystrophy and primary ciliary dyskinesia

Fan

Patel

Yannuzzi

et al. 2019

American Journal of Ophthalmology Case Reports

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Purpose We describe a unique case of CDH3-related hypotrichosis with juvenile macular dystrophy (HJMD) and DNAH5-related primary ciliary dyskinesia (PCD) with progressive vision loss in a young Indian female without positive family history. Both mutations in this patient have not been previously described in the literature. Observations An 11-year-old girl of Indian descent from a consanguineous family presented to our clinic with poor central visual acuity, recurrent sinopulmonary infections, hypotrichosis, and gradual hearing loss. Fundus examination was significant for atrophic retinal pigmented epithelial (RPE) changes involving both the macula and periphery of both eyes with central foveal hypoautofluorescence. Optical coherence tomography (OCT) demonstrated RPE loss and significant disruption of the ellipsoid layer in both eyes. Full-field electrophysiology tests on initial presentation demonstrated low cone amplitude reduced to <70% of normal range without prolongation. OCT angiography of the RPE and choriocapillaris demonstrated possible flow voids in the central macular region of both eyes. Genetic testing showed that the proband was homozygous for variants CDH3 c.1660A > C; p. Thr554Pro and DNAH5 c.6688-1G>T. Conclusion and Importance: We report two novel variants in the CDH3 and DNAH5 genes that are important for future mutational analysis of both HJMD and PCD respectively. A relationship between the cadherin protein dysfunction in CDH3 mutations and the ciliopathy of DNAH5 mutations has not been established. HJMD is known to cause a longitudinal deterioration of cone and rod mediated function, therefore recognizing the symptoms, visual impairment, physical examination, and photographic and electrophysiological findings is crucial in counseling the patient, the family, and fellow clinicians.

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