Whole-exome sequencing identifies a novel missense mutation in EDAR causing autosomal recessive hypohidrotic ectodermal dysplasia with bilateral amastia and palmoplantar hyperkeratosis

Haghighi, Alireza; Nikuei, Pooneh; Haghighi-Kakhki, Hamidreza; Saleh‐Gohari, Nasrollah; Baghestani, Shahram; Krawitz, Peter; Hecht, Jochen; Mundlos, Stefan

doi:10.1111/bjd.12151

Cited by 25 publications

(14 citation statements)

References 11 publications

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“…However, recently identified EDAR mutations demonstrate that pathogenic variants result in variable phenotypes with mild-tosevere clinical manifestations. 5 We report a novel mutation in the EDAR gene in an Italian family with autosomal dominant HED that supports emerging evidence for a genoytype-phenotype correlation. 5 The clinical, genetic and functional studies were conducted according to the Helsinki declaration and written informed consent was obtained from all participating family members; including consent to publish data and clinical images.…”

Section: Identification Of a Novel Frameshift Mutation In The Edar Gesupporting

confidence: 78%

“…5 We report a novel mutation in the EDAR gene in an Italian family with autosomal dominant HED that supports emerging evidence for a genoytype-phenotype correlation. 5 The clinical, genetic and functional studies were conducted according to the Helsinki declaration and written informed consent was obtained from all participating family members; including consent to publish data and clinical images. Three members of the family were available for detailed clinical investigation (V:5; IV:7; IV:5), and four underwent molecular genetic analysis (V:5; IV:7; IV:5; III:2) ( Fig.…”

Section: Identification Of a Novel Frameshift Mutation In The Edar Gesupporting

confidence: 78%

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Identification of a novel frameshift mutation in the EDAR gene causing autosomal dominant hypohidrotic ectodermal dysplasia

Callea

Willoughby

Nieminen

et al. 2014

Acad Dermatol Venereol

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Section: Identification Of a Novel Frameshift Mutation In The Edar Gesupporting

confidence: 78%

Section: Identification Of a Novel Frameshift Mutation In The Edar Gesupporting

confidence: 78%

Identification of a novel frameshift mutation in the EDAR gene causing autosomal dominant hypohidrotic ectodermal dysplasia

Callea

Willoughby

Nieminen

et al. 2014

Acad Dermatol Venereol

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“…The observation of the scalp abnormality in Patient 2 suggests a potential mechanistic connection between KMT2D and KCTD1 , which both code for proteins involved in transcriptional regulation. Additional genes that are associated with abnormal breast development include: (a) TBX3 , which causes Ulnar‐Mammary syndrome (MIM 181450) (M. Bamshad et al, ); (b) TP63 which causes multiple developmental disorders (M. J. Bamshad, ; Rinne, Hamel, van Bokhoven, & Brunner, ); (c) EDA , which causes X‐Linked Hypohidrotic Ectodermal Dysplasia (XLHED) (MIM 305100) (Wahlbuhl‐Becker, Faschingbauer, Beckmann, & Schneider, ); (d) EDAR , which causes autosomal recessive hypohidrotic ectodermal dysplasia (MIM 224900) (Haghighi et al, ); and (e) Figure , which causes Yunis–Varon syndrome (MIM 216340) (Campeau et al, ). Two families with variants that disrupt PTPRF have been reported to have athelia (MIM 616001) (Ausavarat et al, ; Borck et al, ).…”

Section: Discussionmentioning

confidence: 99%

Phenotypic expansion of KMT2D‐related disorder: Beyond Kabuki syndrome

Baldridge

Spillmann

Wegner

et al. 2020

American J of Med Genetics Pt A

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Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads. Most disease-causing variants identified to date are putative loss-of-function alleles, although 15-20% of cases are attributed to missense variants. We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature. These individuals also lack the typical dysmorphic facial features found in Kabuki syndrome. Two of the four patients had severe interstitial lung disease. All of these variants cluster within a 40-amino-acid region of the protein that is located just N-terminal of an annotated coiled coil domain. These findings significantly expand the phenotypic spectrum of features associated with variants in KMT2D beyond those seen in Kabuki syndrome and suggest a possible new underlying disease mechanism for these patients. K E Y W O R D S athelia, Kabuki syndrome, KMT2D

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“…In the literature, Sanger sequencing and multiplex ligation-dependent probe amplification have been commonly used for EDA mutation discovery in both research and clinical studies (Lexner et al, 2008). Recently, whole-exome sequencing has been reported to be an economical and rapid tool for genetic diagnosis, and it has been used to diagnose types of disorders similar to ED (Haghighi et al, 2013). In this study, we performed whole-exome sequencing to screen ED-associated genes in a boy affected with HED, and identified that an EDA (G299D) mutation might be the primary cause of the disorder in this patient.…”

Section: Discussionmentioning

confidence: 99%

EDA mutation as a cause of hypohidrotic ectodermal dysplasia: a case report and review of the literature

Huang¹,

Liang²,

Sui³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Ectodermal dysplasia (ED) represents a collection of rare disorders that result from a failure of development of the tissues derived from the embryonic ectoderm. ED is often associated with hair, teeth, and skin abnormalities, which are serious conditions affecting the quality of life of the patient. To date, a large number of genes have been found to be associated with this syndrome. Here, we report a patient with hypohidrotic ED (HED) without family history. We identified that this patient's disorder arises from an X-linked HED with a mutation in the EDA gene (G299D) found by whole-exome sequencing. In addition, in this paper we summarize the disease-causing mutations based on current literature. Overall, recent clinical and genetic research involving patients with HED have uncovered a large number of pathogenic mutations in EDA, which might contribute to 10345 EDA mutation as a cause of HED ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 10344-10351 (2015) a full understanding of the function of EDA and the underlying mechanisms of HED caused by EDA mutations.

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Whole-exome sequencing identifies a novel missense mutation in EDAR causing autosomal recessive hypohidrotic ectodermal dysplasia with bilateral amastia and palmoplantar hyperkeratosis

Cited by 25 publications

References 11 publications

Identification of a novel frameshift mutation in the EDAR gene causing autosomal dominant hypohidrotic ectodermal dysplasia

Identification of a novel frameshift mutation in the EDAR gene causing autosomal dominant hypohidrotic ectodermal dysplasia

Phenotypic expansion of KMT2D‐related disorder: Beyond Kabuki syndrome

EDA mutation as a cause of hypohidrotic ectodermal dysplasia: a case report and review of the literature

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