A genome-wide significant association on chromosome 15 for congenital entropion in Swiss White Alpine sheep.

Entropion is a known congenital disorder in sheep presumed to be heritable but no causative genetic variant has been reported. Affected lambs show a variable inward rolling of the lower eyelids leading to blindness in severe cases. In Switzerland, the Swiss White Alpine (SWA) breed showed a significantly higher prevalence for entropion than other breeds. A GWAS using 150 SWA sheep (90 affected lambs and 60 controls), based on 600k SNP data, revealed a genome-wide significant signal on chromosome 15. The 0.2 Mb associated region contains functional candidate genes, SMTNL1 and CTNND1. Pathogenic variants in human CTNND1 cause blepharocheilodontic syndrome 2, a rare disorder including eyelid anomalies, and SMTNL1 regulates contraction and relaxation of skeletal and smooth muscle. WGS of a single entropion-affected lamb revealed two private missense variants in SMTNL1 and CTNND1. Subsequent genotyping of both variants in 231 phenotyped SWA sheep was performed. The SMTNL1 variant p.(Asp452Asn) affects an evolutionary conserved residue within an important domain and represents a rare allele, which occurred also in controls. The p.(Glu943Lys) variant in CTNND1 represents a common variant unlikely to cause entropion as the mutant allele occurred more frequently in non-affected sheep. Therefore, we propose that these protein-changing variants are unlikely to explain the phenotype. Additionally, WGS of three further disconcordant pairs of full siblings was carried out but revealed no obvious causative variant. Finally, we conclude that entropion represents a more complex disease caused by different non-coding regulatory variants.

Genome-Wide Association Identifies SLC2A9 and NLN Gene Regions as Associated with Entropion in Domestic Sheep.

Entropion is an inward rolling of the eyelid allowing contact between the eyelashes and cornea that may lead to blindness if not corrected. Although many mammalian species, including humans and dogs, are afflicted by congenital entropion, no specific genes or gene regions related to development of entropion have been reported in any mammalian species to date. Entropion in domestic sheep is known to have a genetic component therefore, we used domestic sheep as a model system to identify genomic regions containing genes associated with entropion. A genome-wide association was conducted with congenital entropion in 998 Columbia, Polypay, and Rambouillet sheep genotyped with 50,000 SNP markers. Prevalence of entropion was 6.01%, with all breeds represented. Logistic regression was performed in PLINK with additive allelic, recessive, dominant, and genotypic inheritance models. Two genome-wide significant (empirical P<0.05) SNP were identified, specifically markers in SLC2A9 (empirical P = 0.007; genotypic model) and near NLN (empirical P = 0.026; dominance model). Six additional genome-wide suggestive SNP (nominal P<1x10(-5)) were identified including markers in or near PIK3CB (P = 2.22x10(-6); additive model), KCNB1 (P = 2.93x10(-6); dominance model), ZC3H12C (P = 3.25x10(-6); genotypic model), JPH1 (P = 4.68x20(-6); genotypic model), and MYO3B (P = 5.74x10(-6); recessive model). This is the first report of specific gene regions associated with congenital entropion in any mammalian species, to our knowledge. Further, none of these genes have previously been associated with any eyelid traits. These results represent the first genome-wide analysis of gene regions associated with entropion and provide target regions for the development of sheep genetic markers for marker-assisted selection.

Case report: entropion and periorbital dermatitis in an Assaf ram.

Entropion and periorbital dermatitis in an Assaf ram are reported. The severe clinical, pathological and histopathological findings are described. Parent animals of concern must be excluded from further breedings as the condition is inherited. The consequences of a such congenital condition in a ram and the recommendations are discussed.

The correction of oriental lower lid involutional entropion using the combined procedure.

INTRODUCTION: Involutional entropion is a common lid malposition problem in the Chinese geriatric population. The major contributing factors of involutional entropion include disinsertion of the lower lid retractors and horizontal lid laxity. The combined procedure (lower lid retractor repair and lateral tarsal strip procedure) is a useful technique that tackles both the horizontal and vertical aetiologic components of this condition. The surgical technique of this procedure is described and the results and complications presented. MATERIALS AND METHODS: A retrospective non-randomised study on 41 lower eyelids of 38 Chinese patients. The combined procedure was performed by a single surgeon over a 2 years 11 months period. Nine patients had bilateral lid surgeries. The clinical charts and operative notes were reviewed by an observer. RESULTS: The mean age of the patients was 74.7 years (range 51 to 92 years). There were 14 males (36.8%) and 24 females (63.2%). The cases were followed up postoperatively for a mean duration of 13 months (range 3 to 48 months). Twelve lids had early postoperative overcorrection but the majority (8 lids) resolved spontaneously with good lid-globe apposition. Of the remaining 4 eyelids, 3 lids had persistent mild asymptomatic ectropion that did not require surgical treatment and only one required re-operation. CONCLUSION: The combined procedure is an effective means of repair for oriental lower lid entropion with low complication rates.

Report of a family with dominantly inherited upper lid entropion.

AIM: To report the occurrence of late onset, bilateral, idiopathic upper lid entropion, occurring in three members of the same family, with a known family history. METHODS: Five family members were examined, and a history taken, at Moorfields Eye Hospital. Three patients were treated surgically, and one also had a tarsoconjunctival biopsy. RESULTS: In all cases, no aetiology was found. The family history suggests an autosomal dominant inheritance pattern. All patients were treated with anterior lamellar repositioning, and had optimal results. CONCLUSION: The family reported seems to be affected by a familial form of primary acquired upper lid entropion, that shows an autosomal dominant inheritance pattern.

Ophthalmic manifestations of ectrodactyly-ectodermal dysplasia-clefting syndrome.

Ophthalmic manifestations are a common component of the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome; however, few ophthalmic publications have specifically addressed these features. The authors describe a 38-year-old patient with EEC syndrome who demonstrated several associated ocular signs and symptoms. The ophthalmic findings in this patient included bilateral entropion with secondary trichiasis, and shallow inferior fornices with symblepharon. Interestingly, the patient also had vertically deficient tarsi and absence of the meibomian glands. Ophthalmologists should be aware of the ocular signs and symptoms associated with EEC because some manifestations can potentially be sight threatening.

Clinical characteristics of CHARGE syndrome.

CHARGE syndrome, first described by Pagon, was named for its six major clinical features. They are: coloboma of the eye, heart defects, atresia of the choanae, retarded growth and development including CNS anomalies, genital hypoplasia and/or urinary tract anomalies, and ear anomalies and/or hearing loss. We experienced three cases of CHARGE syndrome who displayed ocular coloboma, heart defects, retarded growth and development, and external ear anomalies, and we also review the previously reported literature concerning CHARGE syndrome.

Clinical characteristics of CHARGE syndrome

CHARGE syndrome, first described by Pagon, was named for its six major clinical features. They are: coloboma of the eye, heart defects, atresia of the choanae, retarded growth and development including CNS anomalies, genital hypoplasia and/or urinary tract anomalies, and ear anomalies and/or hearing loss. We experienced three cases of CHARGE syndrome who displayed ocular coloboma, heart defects, retarded growth and development, and external ear anomalies, and we also review the previously reported literature concerning CHARGE syndrome.

Skin diseases of the Chinese Shar-Pei.

This article deals with the unique skin disorders seen only in the Shar-Pei. The difference between skin diseases in Shar-Pei and other breeds is described. Prevention and treatment are discussed. Suggestions are given to alter the breed's anatomy slightly to decrease the genetic predisposition to certain dermatoses.

[Entropion in newborn lambs]. / Das Entropium bei neugeborenen Lämmern.

The Entropion in newborn lambs could be proved so far in 8 sheep-breeds and 7 cross-breeds out of 33 flocks in the Federal Republic of Germany. In our patients the Entropion was found at the lower eyelid only. The owners of the animals often mistake the Entropion for an ophthalmia. An early diagnosis and an early beginning of the therapy keep the expenditure of treatment small and shorten the period of treatment; therefore examination is commendable within a short time after birth. Female lambs get clearly more often affected than male ones (Gynecotropia). In small pure-bred flocks with only one breeding-ram (and also in breeds with a limited population) the percentage of suffering lambs is higher than in large and crossed flocks with several rams and in large populations (except the breed "Heidschnucke"). In agreement with the literature it must be supposed that different genes are responsible for the Entropion. The selection of ill animals and those which are suspected of transmitting the disposition is evidently appropriate to lower the number of attacks of illness within a population considerably. All 47 affected eyes of 32 lambs were treated. Low degrees of Entropion were healed by repeated manual eversion plus application of antibiotic eye-ointment. In middle and high degrees of Entropion the application of Michel-wound-clamps on 23 of 26 eyes was successful; antibiotic eye-ointment was applied here, too; additionally these lambs prophylactically got 2000 I.U. of Tetanus-antitoxin.(ABSTRACT TRUNCATED AT 250 WORDS)