Letters to the Editor
CONFLICT OF INTEREST:
None declared.
Mari TANAKA,1,* Liping YANG,1,* Mari WATAYAKANEDA,1 Tamio SUZUKI,2 Ken OKAMURA,2 Yutaka HOZUMI,2 Fei YANG,1 Ichiro KATAYAMA1 1
Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, and 2Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan doi: 10.1111/1346-8138.12937
REFERENCES
2 Cullinane AR, Curry JA, Carmona-Rivera C et al. A BLOC-1 mutation screen reveals that PLDN is mutated in Hermansky-Pudlak Syndrome type 9. Am J Hum Genet 2011; 88: 778–787. 3 Nazarian R, Falcon-Perez JM, Dell’Angelica EC. Biogenesis of lysosome-related organelles complex 3 (BLOC-3): a complex containing the Hermansky-Pudlak syndrome (HPS) proteins HPS1 and HPS4. Proc Natl Acad Sci USA 2003; 100: 8770–8775. 4 Suzuki T, Ito S, Inagaki K et al. Investigation on the IVS5 + 5G –> a splice site mutation of HPS1 gene found in Japanese patients with Hermansky-Pudlak syndrome. J Dermatol Sci 2004; 36: 106– 108. 5 Natsuga K, Akiyama M, Shimizu T et al. Ultrastructural features of trafficking defects are pronounced in melanocytic nevus in Hermansky-Pudlak syndrome type 1. J Invest Dermatol 2005; 125: 154– 158.
1 Okamura K, Yoshizawa J, Abe Y et al. Oculocutaneous albinism (OCA) in Japanese patients: five novel mutations. J Dermatol Sci 2014; 74: 173–174.
Case of X-linked hypohidrotic ectodermal dysplasia with a novel EDA missense mutation Dear Editor, X-linked hypohidrotic ectodermal dysplasia (XLHED; Mendelian Inheritance in Man no. 305100) is the most common form of ectodermal dysplasia, and is caused by a variety of EDA gene mutations. The EDA gene encodes ectodysplasin-A, a protein that belongs to the tumor necrosis factor ligand superfamily.1 A 6-year-old Japanese boy presented with recurrent episodes of high body temperature during the summer. He had manifested xerosis and dermatitis shortly after birth, and he was treated based on a diagnosis of atopic dermatitis. He also presented with sparse, thin hair and eyebrows, a prominent forehead and a saddle nose (Fig. 1a); moreover, he only had two teeth (Fig. 1b), but his nails were normal. He presented the typical XLHED triad symptoms, namely, hypodontia, hypotrichosis and hypohidrosis. Additionally, he had dry skin and lichenificated erythema on his neck (Fig. 1c) and cubital and popliteal fossae. Laboratory data showed an elevated eosinophil count (845/lL; 8.9% of the total leukocytes) and an elevated serum immunoglobulin E level (1601.2 IU/mL). Histological findings of a skin biopsy from the patient’s upper back included the absence of hair follicles and sweat glands (Fig. 1d). His father and sister also had atopic dermatitis and his mother’s skin was xerotic. Otherwise, none of his family members demonstrated any abnormal features. Based on these findings, we diagnosed him as having XLHED with atopic dermatitis. An EDA mutation analysis in the proband genomic DNA was performed, as previously described, after obtaining written informed consent.2 A direct sequencing mutation analysis revealed a missense mutation, c.146T>A, in exon 1a of the EDA gene (Fig. 1e). His mother
and sister had the same, but heterozygous, missense mutation. This mutation is reported to result in a change from leucine to histidine at amino acid residue 49 (p.L49H) in the ectodysplasin-A transmembrane domain. Restriction enzymes were used to detect the restriction fragment length polymorphism (RFLP) pattern of the EDA exon 1a. The 262-bp polymerase chain reaction-amplified DNA product was analyzed using the Mse I restriction enzyme. Mse I recognizes the missense mutation sequence, but not the wild-type sequence (Fig. 1f). RFLP has indicated that the c.146T>A mutation in the EDA gene is not a common polymorphism. Two hundred and forty-nine EDA mutations have been reported (Human Gene Mutation Database: http:// www.hgmd.cf.ac.uk/), including 129 missense mutations. Most patients with these mutations exhibit the typical hypohidrotic ectodermal dysplasia triad of symptoms and display characteristic facial features. The abnormal development of sweat glands is assumed to cause dry skin and impaired epidermal barrier function, which may be responsible for the atopic diathesis.3 A previously reported missense mutation (c.146T>C) results in a change from leucine to proline at amino acid residue 49 (p.L49P).4 However, despite the absence of sweat glands, that patient did not have a history of eczema or atopic dermatitis, but had dry eyes. In contrast, our patient had atopic dermatitis, which may be associated with his other genetic background and/or environmental factors. The accumulation of case reports describing the genotype and phenotype of XLHED patients will contribute to a better understanding of the function of ectodysplasin-A.
Correspondence: Masahito Yasuda, M.D., Ph.D., Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan. Email: [email protected]
© 2015 Japanese Dermatological Association
907
Letters to the Editor
(a)
(c)
Figure 1. Patient clinical and histological findings. Physical examination revealed (a) sparse, thin hair and eyebrows, a prominent forehead, periorbital pigmentation, a saddle nose, (b) hypodontia and (c) lichenificated erythema on the nuchal region. (d) A biopsy specimen showed the absence of hair follicles and sweat glands (hematoxylin–eosin, original magnification 9100). Detection and segregation of the EDA gene mutation. (e) The patient has a missense mutation at nucleotide 146 (c.146T>A) resulting in p.L49H. His mother and sister are heterozygosis for the same mutation. (f) The Mse I digestion patterns of the polymerase chain reaction (PCR) products for the patient (lane 2), mother (lane 3), sister (lane 4) and normal controls (lanes 5–9); lane 1 shows the molecular weight markers. The 262-bp band indicates a normal allele, whereas the 205- and 57-bp bands indicate mutant alleles. PCR products from 30 healthy controls were analyzed.
(b)
(d)
CONFLICT OF INTEREST:
None.
Masahito YASUDA, Chikako KISHI, Yoko YOKOYAMA, Hiroo AMANO, Osamu ISHIKAWA Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan doi: 10.1111/1346-8138.12959
(e)
REFERENCES
(f)
1 Kere J, Srivastava AK, Montonen O et al. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet 1996; 13: 409–416. 2 Gunadi , Miura K, Ohta M et al. Two novel mutations in the ED1 gene in Japanese families with X-linked hypohidrotic ectodermal dysplasia. Pediatr Res 2009; 65: 453–457. 3 Koguchi-Yoshioka H, Wataya-Kaneda M, Yutani M et al. Atopic diathesis in hypohidrotic/anhidrotic ectodermal dysplasia. Acta Derm Venereol 2015; 95: 476–479. 4 Dietz J, Kaercher T, Schneider AT et al. Early respiratory and ocular involvement in X-linked hypohidrotic ectodermal dysplasia. Eur J Pediatr 2013; 172: 1023–1031.
Case of pachydermoperiostosis with solute carrier organic anion transporter family, member 2A1 (SLCO2A1) mutations Dear Editor, The major diagnostic criteria for pachydermoperiostosis (PDP), or primary hypertrophic osteoarthropathy (Mendelian Inheritance in Man no. 167100), are finger clubbing, periostosis, pachydermia and cutis verticis gyrata.1,2 Additional reported symptoms include sebaceous hyperplasia, hyperhidrosis and arthropathy.1,2 A diagnosis of PDP is usually made in patients aged older than 20 years. Here, we report a case of PDP diagnosed at puberty.
A 15-year-old Japanese boy was referred to Hirosaki University School of Medicine and Hospital. His symptoms included clubbing of the fingers and toes, and greasiness of the facial skin, although only faint pachydermia was noted (Fig. 1a,b). His sibling and parents did not display associated symptoms. He started to notice enlargement of his fingers and toes at the age of 12 years. Subsequently, he experienced pain in his shoulder and knee joints. Endocrinological examinations showed no notable evidence of acromegaly. Radiological
Correspondence: Satoko Minakawa, M.D., Ph.D., and Daisuke Sawamura, M.D., Ph.D., Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan. Emails: [email protected] and [email protected]
908
© 2015 Japanese Dermatological Association
CONFLICT OF INTEREST:
None declared.
Mari TANAKA,1,* Liping YANG,1,* Mari WATAYAKANEDA,1 Tamio SUZUKI,2 Ken OKAMURA,2 Yutaka HOZUMI,2 Fei YANG,1 Ichiro KATAYAMA1 1
Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, and 2Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan doi: 10.1111/1346-8138.12937
REFERENCES
2 Cullinane AR, Curry JA, Carmona-Rivera C et al. A BLOC-1 mutation screen reveals that PLDN is mutated in Hermansky-Pudlak Syndrome type 9. Am J Hum Genet 2011; 88: 778–787. 3 Nazarian R, Falcon-Perez JM, Dell’Angelica EC. Biogenesis of lysosome-related organelles complex 3 (BLOC-3): a complex containing the Hermansky-Pudlak syndrome (HPS) proteins HPS1 and HPS4. Proc Natl Acad Sci USA 2003; 100: 8770–8775. 4 Suzuki T, Ito S, Inagaki K et al. Investigation on the IVS5 + 5G –> a splice site mutation of HPS1 gene found in Japanese patients with Hermansky-Pudlak syndrome. J Dermatol Sci 2004; 36: 106– 108. 5 Natsuga K, Akiyama M, Shimizu T et al. Ultrastructural features of trafficking defects are pronounced in melanocytic nevus in Hermansky-Pudlak syndrome type 1. J Invest Dermatol 2005; 125: 154– 158.
1 Okamura K, Yoshizawa J, Abe Y et al. Oculocutaneous albinism (OCA) in Japanese patients: five novel mutations. J Dermatol Sci 2014; 74: 173–174.
Case of X-linked hypohidrotic ectodermal dysplasia with a novel EDA missense mutation Dear Editor, X-linked hypohidrotic ectodermal dysplasia (XLHED; Mendelian Inheritance in Man no. 305100) is the most common form of ectodermal dysplasia, and is caused by a variety of EDA gene mutations. The EDA gene encodes ectodysplasin-A, a protein that belongs to the tumor necrosis factor ligand superfamily.1 A 6-year-old Japanese boy presented with recurrent episodes of high body temperature during the summer. He had manifested xerosis and dermatitis shortly after birth, and he was treated based on a diagnosis of atopic dermatitis. He also presented with sparse, thin hair and eyebrows, a prominent forehead and a saddle nose (Fig. 1a); moreover, he only had two teeth (Fig. 1b), but his nails were normal. He presented the typical XLHED triad symptoms, namely, hypodontia, hypotrichosis and hypohidrosis. Additionally, he had dry skin and lichenificated erythema on his neck (Fig. 1c) and cubital and popliteal fossae. Laboratory data showed an elevated eosinophil count (845/lL; 8.9% of the total leukocytes) and an elevated serum immunoglobulin E level (1601.2 IU/mL). Histological findings of a skin biopsy from the patient’s upper back included the absence of hair follicles and sweat glands (Fig. 1d). His father and sister also had atopic dermatitis and his mother’s skin was xerotic. Otherwise, none of his family members demonstrated any abnormal features. Based on these findings, we diagnosed him as having XLHED with atopic dermatitis. An EDA mutation analysis in the proband genomic DNA was performed, as previously described, after obtaining written informed consent.2 A direct sequencing mutation analysis revealed a missense mutation, c.146T>A, in exon 1a of the EDA gene (Fig. 1e). His mother
and sister had the same, but heterozygous, missense mutation. This mutation is reported to result in a change from leucine to histidine at amino acid residue 49 (p.L49H) in the ectodysplasin-A transmembrane domain. Restriction enzymes were used to detect the restriction fragment length polymorphism (RFLP) pattern of the EDA exon 1a. The 262-bp polymerase chain reaction-amplified DNA product was analyzed using the Mse I restriction enzyme. Mse I recognizes the missense mutation sequence, but not the wild-type sequence (Fig. 1f). RFLP has indicated that the c.146T>A mutation in the EDA gene is not a common polymorphism. Two hundred and forty-nine EDA mutations have been reported (Human Gene Mutation Database: http:// www.hgmd.cf.ac.uk/), including 129 missense mutations. Most patients with these mutations exhibit the typical hypohidrotic ectodermal dysplasia triad of symptoms and display characteristic facial features. The abnormal development of sweat glands is assumed to cause dry skin and impaired epidermal barrier function, which may be responsible for the atopic diathesis.3 A previously reported missense mutation (c.146T>C) results in a change from leucine to proline at amino acid residue 49 (p.L49P).4 However, despite the absence of sweat glands, that patient did not have a history of eczema or atopic dermatitis, but had dry eyes. In contrast, our patient had atopic dermatitis, which may be associated with his other genetic background and/or environmental factors. The accumulation of case reports describing the genotype and phenotype of XLHED patients will contribute to a better understanding of the function of ectodysplasin-A.
Correspondence: Masahito Yasuda, M.D., Ph.D., Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan. Email: [email protected]
© 2015 Japanese Dermatological Association
907
Letters to the Editor
(a)
(c)
Figure 1. Patient clinical and histological findings. Physical examination revealed (a) sparse, thin hair and eyebrows, a prominent forehead, periorbital pigmentation, a saddle nose, (b) hypodontia and (c) lichenificated erythema on the nuchal region. (d) A biopsy specimen showed the absence of hair follicles and sweat glands (hematoxylin–eosin, original magnification 9100). Detection and segregation of the EDA gene mutation. (e) The patient has a missense mutation at nucleotide 146 (c.146T>A) resulting in p.L49H. His mother and sister are heterozygosis for the same mutation. (f) The Mse I digestion patterns of the polymerase chain reaction (PCR) products for the patient (lane 2), mother (lane 3), sister (lane 4) and normal controls (lanes 5–9); lane 1 shows the molecular weight markers. The 262-bp band indicates a normal allele, whereas the 205- and 57-bp bands indicate mutant alleles. PCR products from 30 healthy controls were analyzed.
(b)
(d)
CONFLICT OF INTEREST:
None.
Masahito YASUDA, Chikako KISHI, Yoko YOKOYAMA, Hiroo AMANO, Osamu ISHIKAWA Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan doi: 10.1111/1346-8138.12959
(e)
REFERENCES
(f)
1 Kere J, Srivastava AK, Montonen O et al. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet 1996; 13: 409–416. 2 Gunadi , Miura K, Ohta M et al. Two novel mutations in the ED1 gene in Japanese families with X-linked hypohidrotic ectodermal dysplasia. Pediatr Res 2009; 65: 453–457. 3 Koguchi-Yoshioka H, Wataya-Kaneda M, Yutani M et al. Atopic diathesis in hypohidrotic/anhidrotic ectodermal dysplasia. Acta Derm Venereol 2015; 95: 476–479. 4 Dietz J, Kaercher T, Schneider AT et al. Early respiratory and ocular involvement in X-linked hypohidrotic ectodermal dysplasia. Eur J Pediatr 2013; 172: 1023–1031.
Case of pachydermoperiostosis with solute carrier organic anion transporter family, member 2A1 (SLCO2A1) mutations Dear Editor, The major diagnostic criteria for pachydermoperiostosis (PDP), or primary hypertrophic osteoarthropathy (Mendelian Inheritance in Man no. 167100), are finger clubbing, periostosis, pachydermia and cutis verticis gyrata.1,2 Additional reported symptoms include sebaceous hyperplasia, hyperhidrosis and arthropathy.1,2 A diagnosis of PDP is usually made in patients aged older than 20 years. Here, we report a case of PDP diagnosed at puberty.
A 15-year-old Japanese boy was referred to Hirosaki University School of Medicine and Hospital. His symptoms included clubbing of the fingers and toes, and greasiness of the facial skin, although only faint pachydermia was noted (Fig. 1a,b). His sibling and parents did not display associated symptoms. He started to notice enlargement of his fingers and toes at the age of 12 years. Subsequently, he experienced pain in his shoulder and knee joints. Endocrinological examinations showed no notable evidence of acromegaly. Radiological
Correspondence: Satoko Minakawa, M.D., Ph.D., and Daisuke Sawamura, M.D., Ph.D., Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan. Emails: [email protected] and [email protected]
908
© 2015 Japanese Dermatological Association
