Hypotrichosis with juvenile macular dystrophy: Portuguese case

Elfatoiki, Fatima Zahra; Cordoliani, F; Regane, Pascal Pascal; Affortit-Demoge, Aude; Rybojad, M.

doi:10.7241/ourd.2020e.20

Cited by 3 publications

(4 citation statements)

References 6 publications

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“…Hypotrichosis with juvenile macular dystrophy is a rare congenital disease mainly found in the Druze population of Northern Israel and close by Mediterranean areas (Elfatoiki, Cordoliani, Pascal Regane, & Afforitit‐Demoge, ). We report here, to our knowledge for the first time, an intragenic Alu ‐mediated deletion causing HJMD that results in the homozygous loss of the entire exon 3 in CDH3 .…”

Section: Discussionmentioning

confidence: 99%

Hypotrichosis with juvenile macular dystrophy: Combination of whole‐genome sequencing and genome‐wide homozygosity mapping identifies a large deletion in CDH3 initially undetected by whole‐exome sequencing—A lesson from next‐generation sequencing

Saeidian

Vahidnezhad

Youssefian

et al. 2019

Molec Gen & Gen Med

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BackgroundHypotrichosis with juvenile macular dystrophy (HJMD) is an autosomal recessive disorder characterized by abnormal growth of scalp hair and juvenile macular degeneration leading to blindness. We have explored the genetic basis of HJMD in a large consanguineous family with 12 affected patients, 1–76 years of age, with characteristic phenotypes.MethodsWe first applied genome‐wide homozygosity mapping to 10 affected individuals for linkage analysis to identify the genomic region of the defective gene. All affected individuals shared a 7.2 Mb region of homozygosity on chromosome 16q21‐22.3, which harbored 298 genes, including CDH3, previously associated with HJMD. However, whole‐exome sequencing (WES) failed to identify the causative mutation in CDH3.ResultsFurther investigation revealed a missense variant in a gene closely linked to CDH3 (1.4 Mb distance: FHOD1: c.1306A>G, p.Arg436Gly). This variant was homozygous in all affected individuals and heterozygous in 18 out of 19 obligate carriers. While this variant was found by bioinformatics predictions to be likely pathogenic, a knock‐in mouse for this variant, made by the CRISPR/Cas, showed no disease phenotype. However, using whole‐genome sequencing (WGS), we were able to identify a novel Alu recombination‐mediated deletion in CDH3:c.del161‐811_246 + 1,044.ConclusionWGS was able to identify a deep intronic deletion mutation, not detected by WES.

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Section: Discussionmentioning

confidence: 99%

Hypotrichosis with juvenile macular dystrophy: Combination of whole‐genome sequencing and genome‐wide homozygosity mapping identifies a large deletion in CDH3 initially undetected by whole‐exome sequencing—A lesson from next‐generation sequencing

Saeidian

Vahidnezhad

Youssefian

et al. 2019

Molec Gen & Gen Med

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“…Congenital hypotrichosis associated with juvenile macular dystrophy (MIM 601553) is a rare autosomal recessive disorder characterized by early hair loss, heralding progressive degeneration of the retinal macula leading to early blindness during the second to third decade of life [23,24]. HJMD prevalence is unknown and has only been reported in approximately 30 patients [25][26][27][28][29][30]. Sprecher et al [23] used mapping in four consanguineous families to localize the gene defective in HJMD to 16q22.1.…”

Section: Hypotrichosis With Juvenile Macular Dystrophymentioning

confidence: 99%

“…Significant inter-and intrafamilial differences in hair morphology were found, as well as differences in associated skin findings, severity, and age of onset of visual disability [32]. It has been recommended that all patients with congenital hypotrichosis should undergo a thorough fundus examination [26,27,33,33]. A therapeutic window for gene augmentation therapy to preserve visual acuity was suggested.…”

Section: Hypotrichosis With Juvenile Macular Dystrophymentioning

confidence: 99%

Genetic Hair Disorders: A Review

Ahmed

Almohanna

Griggs

et al. 2019

Dermatol Ther (Heidelb)

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Hair loss in early childhood represents a broad differential diagnosis which can be a diagnostic and therapeutic challenge for a physician. It is important to consider the diagnosis of a genetic hair disorder. Genetic hair disorders are a large group of inherited disorders, many of which are rare. Genetic hair abnormalities in children can be an isolated phenomenon or part of genetic syndromes. Hair changes may be a significant finding or even the initial presentation of a syndrome giving a clue to the diagnosis, such as Netherton syndrome and trichothiodystrophy. Detailed history including family history and physical examination of hair and other ectodermal structures such as nails, sweat glands, and sebaceous glands with the use of dermoscopic devices and biopsy all provide important clues to establish the correct diagnosis. Understanding the pathophysiology of genetic hair defects will allow for better comprehension of their treatment and prognosis. For example, in patients with an isolated hair defect, the main problem is aesthetic. In contrast, when the hair defect is associated with a syndrome, the prognosis will depend mainly on the associated condition. Treatment of many genetic hair disorders is focused on treating the primary cause and minimizing trauma to the hair.

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“…[1] It is associated with mutations in the cadherin 3 (CDH3) gene, resulting in the abnormal expression of P-cadherin. [2]…”

Section: Introductionmentioning

confidence: 99%