- Email: [email protected]
The H syndrome: Two novel mutations affecting the same amino acid residue of hENT3
Letters to the Editor / Journal of Dermatological Science 57 (2010) 57–73 [2] Imokawa G. A possible mechanism underlying the ceramide deficiency in atopic dermatitis: expression of a deacylase enzyme that cleaves the N-acyl linkage of sphingomyelin and glucosylceramide. J Dermatol Sci 2009;55: 1–9. [3] Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A. Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol 1991;96:523–6. [4] Kim HJ, Kim H, Han ES, Park SM, Koh JY, Kim KM, et al. Characterizations of sphingosylphosphorylcholine-induced scratching responses in ICR mice using naltrexon, capsaicin, ketotifen and Y-27632. Eur J Pharmacol 2008; 583:92–6. [5] Andoh T, Saito A, Kuraishi Y. Leukotriene B(4) mediates sphingosylphosphorylcholine-induced itch-associated responses in mouse skin. J Invest Dermato )2009;(August). [6] Hashimoto T, Ohata H, Honda K. Lysophosphatidic acid (LPA) induces plasma exudation and histamine release in mice via LPA receptors. J Pharmacol Sci 2006;100:82–7. [7] Hashimoto T, Ohata H, Momose K, Honda K. Lysophosphatidic acid induces histamine release from mast cells and skin fragments. Pharmacology 2005;75: 13–20. [8] Inagaki N, Igeta K, Kim JF, Nagao M, Shiraishi N, Nakamura N, et al. Involvement of unique mechanisms in the induction of scratching behavior in BALB/c mice by compound 48/80. Eur J Pharmacol 2002;448: 175–83. [9] Nixon GF, Mathieson FA, Hunter I. The multi-functional role of sphingosylphosphorylcholine. Prog Lipid Res 2008;47:62–75. [10] Kim HJ, Kim DK, Kim H, Koh JY, Kim KM, Noh MS, et al. Involvement of the BLT2 receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice. Br J Pharmacol 2008;154:1073–8.
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Hyoung-June Kim Kwang-Mi Kim Jae-Young Koh Min-Soo Noh Amore Pacific Corporation, 314-1 Boradong Giheung-gu, Yongin-si, Gyeonggi-do 449-729, Republic of Korea Mi-Kyung Park Hye-Ja Lee Soo-Youl Kim Chang-Hoon Lee* National Cancer Center, 809 Madu 1-dong, Goyang-si, Gyeonggi-do 416-769, Republic of Korea *Corresponding
author at: National Cancer Center, Molecular Oncology Branch, 809 Madu 1-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do, 416-769, Republic of Korea. Tel.: +82 31 920 2222/2232; fax: +82 31 920 2006 E-mail addresses: [email protected] [email protected] (C-H. Lee) 4 May 2009
doi:10.1016/j.jdermsci.2009.09.007
Letter to the Editor The H syndrome: Two novel mutations affecting the same amino acid residue of hENT3 H syndrome (OMIM 612391) is a recently described autosomalrecessive genodermatosis with systemic manifestations. The disease is characterized by the major clinical findings of progressive cutaneous hyperpigmentation and hypertrichosis located mainly over the lower limbs and lower abdomen, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height and hyperglycemia/diabetes mellitus [1,2]. The major histopathological findings include dermal infiltrate consisting mainly of histiocytes, later replaced by dermal and subcutaneous fibrosis [3]. Recently, we [2] and others [4] found that missense, nonsense, compound and deletion mutations in the SLC29A3 gene are responsible for this unique clinical picture. The SLC29A3 gene encodes the human equilibrative nucleoside transporter (hENT3), which mediates passive sodium-independent transport of nucleosides [5]. The exact cellular localization of hENT3, endosomal/lysosomal [6] or mitochondrial [7], and its function with relation to the H syndrome is still unclear. Here, we report two new cases of H syndrome, of Spanish and of Arab origin and describe two novel missense mutations. Patient 1 is a 13-year-old male, originating from a nonconsanguineous Spanish family (Fig. 1D). He first presented at the age of 4-year-old with an enlarging cutaneous mass over his left thigh with sclerodermoid induration and slight hyperpigmentation and hypertrichosis. Over the years the cutaneous changes gradually spread to involve the left shin, left lower abdomen and right thigh (Fig. 1A). Progressive bilateral sensorineural hearing loss presented when the patient was eight. At age 10 he developed diffuse alopecia of the scalp and halo nevi on the trunk. Additional significant findings on physical examination included gynecomastia (Fig. 1A), splenomegaly, scrotal masses, varicose veins and fixed flexion contractures of the proximal interphalangeal joint of his left fifth finger (Fig. 1A). Several weeks of prednisone treatment induced partial improvement of the thickened and indurated thigh masses and abdominal plaques.
Patient 2 is a 20-year-old male, originating from a consanguineous Arab family (Fig. 1D). He presented with hearing loss since age 4 and cutaneous induration and hyperpigmentation of the thighs which first appeared when he was 8-year-old and gradually extended to the genitals, back and lower limbs with overlying hypertrichosis. On physical examination, short stature (128 cm) and dysmorphic facies with downslanting palpebral fissures, short nose, anteverted nares and retrognathism were seen. Additional findings included arcus senilis, scrotal masses, hepatosplenomegaly and fixed flexion contractures of the proximal interphalangeal joints of the right fourth and fifth fingers and the left fifth finger. Informed consent for affected individuals and their family members was obtained and DNA was extracted from peripheral blood leukocytes using a commercial kit (Gentra System Inc., Minneapolis, MN). All SLC29A3 exons and splice junctions were PCR-amplified using intronic primers, as previously described [2]. PCR products were purified and sequenced on ABI 3700 capillary sequencer (Applied Biosystems, Foster City, CA). Important laboratory findings in both patients included mild microcytic anemia, elevated ESR and CRP, normal glucose level and liver function tests, and no paraprotein. Imaging (US/CT) demonstrated splenomegaly and/or hepatomegaly and lymphadenopathy. The major histological findings in skin biopsy included dermal infiltrate consisting of lymphocytes, plasma cells and CD68+ histiocytes, and dermal and subcutaneous fibrosis (Fig. 1B and C). In the Spanish patient a novel c.1087C>T missense mutation in exon 6 was found, changing arginine 363 to tryptophan (p.Arg363Trp) (Fig. 2A). In the Arab patient, another novel missense mutation, c.1088G>A, was found affecting the same amino acid residue as in patient 1, changing arginine 363 to glutamine (p.Arg363Gln) (Fig. 2A). These mutations were not detected in 100 Spanish and 102 Arab controls, respectively, suggesting this is not a common polymorphism. The clinical presentation and pathological findings of both patients are similar to the previously reported patients [1–4,8–10]. It is of interest that patient 1 had several unique clinical features: multiple halo nevi and diffuse scalp alopecia, consistent histolo-
60
Letters to the Editor / Journal of Dermatological Science 57 (2010) 57–73
Fig. 1. Pedigrees, clinical and histological findings in H syndrome patients. Clinical findings of patient 1 (A). (1) Extensive hyperpigmentation over lower abdomen, inguinal area and thighs. Scrotal masses are also noted. (2) Fixed flexion contracture of the proximal interphalangeal joint of the left fifth finger. (3) Prominent gynecomastia and dilated veins over abdominal wall. Histological findings of involved skin of left thigh in patient 1 showing dermal fibrosis extending to the subcutis (B), and an extensive histiocytic and dendritic infiltrate (C) (H&E stain, original magnifications 40, 200). (D) 1. Pedigree of patient 1. 2. Pedigree of patient 2. Affected male individuals are indicated in gray.
Fig. 2. (A) Sequence analysis of exon 6 of the SLC29A3 gene in patients 1 and 2: (top left to right) homozygous c.1087C>T mutation (patient 1), c.1088G>A (patient 2), and wild type. (Bottom) heterozygous state. (B) Evolutionary conservation of codon 363 in the SLC29A3 gene, coding in all species for arginine. Mutated nucleotide positions are shown by an arrow.
Letters to the Editor / Journal of Dermatological Science 57 (2010) 57–73
gically with alopecia areata, which were not previously reported in H syndrome, but may be incidental and unrelated to the disorder. It should also be noted that Cliffe et al. [4] described their patients as suffering from an allelic disorder to the H syndrome. Nevertheless, the clinical manifestations are identical. Distinguishing these disorders according to severity of flexion contractures, presence or absence of diabetes mellitus or deafness is artificial, and the differences in the clinical presentation are only due to phenotypic variability. Patients homozygous for the same mutation (e.g. G427S) may present with or without diabetes mellitus and/or deafness or any other feature characteristic of the H syndrome. Both novel mutations described in this report reside in the sixth exon of SLC29A3 and are located in a highly evolutionarily conserved position in the protein (Fig. 2B), between the eighth and ninth transmembranous domains of the transporter. Eight out of nine reported mutations were found in the sixth exon of the gene [2,4 and this report] indicating the importance of this coding region to the function of the transporter and the importance of initial screening of this exon for mutation’s detection in SLC29A3. The ENT family mediates the provision of nucleosides and nucleobases, derived from diet or produced by tissues for salvage pathways of nucleotide synthesis in cells deficient in de novo biosynthetic pathways. Nucleosides and nucleobases are converted in the cell by these salvage pathways to nucleotides which function in intermediary metabolism and as precursors for nucleic acid synthesis. By influencing adenosine concentration in the cell, ENTs also affect many physiological processes. It is not yet known why there are multiple nucleoside and nucleobase transporters with overlapping functions, but it is clear that hENT3 has an essential role in the normal function of multiple cell types and tissues uncompensated by other ENTs, as evident by the diverse clinical phenotype of H syndrome patients. In conclusion, two new patients with H syndrome are described, another patient of Arab origin, and the first of Spanish ancestry. Further recognition and awareness of the disorder will lead to the identification of more patients throughout the world. We anticipate that the study of these patients may better define the clinical spectrum of this unique syndrome, and will shed light on its pathogenesis. Acknowledgments We thank the family members for their participation in this study, and Sofia Babay for expert technical assistance. Funding sources: Authority for Research and Development, Hebrew University of Jerusalem (A.Z.), the Hadassah Medical Center physician scientist program and the Hadassah-Hebrew University Joint Research Fund (V.M.P.). References [1] Molho-Pessach V, Agha Z, Aamar S, Glaser B, Doviner V, Hiller N, et al. The H syndrome: a new genodermatosis characterized by indurated, hyperpigmented and hypertrichotic skin with systemic manifestations. J Am Acad Dermatol 2008;59:79–85. [2] Molho-Pessach V, Lerer I, Abeliovich D, Agha Z, Abu Libdeh A, Broshtilova V, et al. The H syndrome is caused by mutations in the nucleoside transporter hENT3. Am J Hum Genet 2008;83:529–34. [3] Doviner V, Maly A, Ne’eman, Z, Qawasmi R, Aamar S, Sultan M, et al. Syndrome: recently defined genodermatosis with distinct histologic features. A morphologic, histochemical, immunohistochemical and ultrastructural study of ten cases. Am J Dermatopathol; in press. [4] Cliffe ST, Kramer JM, Hussain K, Robben JH, de Jong EK, de Brouwer AP, et al. The SLC29A3 gene is mutated in pigmented hypertrichosis with insulin dependent diabetes mellitus syndrome and intersects with the insulin signaling pathway. Hum Mol Genet 2009;18:2257–65. [5] Hyde RJ, Cass CE, Young JD, Baldwin SA. The ENT family of eukaryote nucleoside and nucleobase transporters: Recent advances in the investigation of structure/function relationships and the identification of novel isoforms. Mol Membr Biol 2001;18:53–63.
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[6] Baldwin SA, Yao SY, Hyde RJ, Ng AML, Foppolo S, Barnes K, et al. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J Biol Chem 2005;280:15880–7. [7] Govindarajan R, Leung GP, Zhou M, Tse CM, Wang J, Unadkat JD. Facilitated mitochondrial import of anti-viral and anti-cancer nucleoside drugs by human equilibrative nucleoside transporter-3 (hENT3). Am J Physiol Gastrointest Liver Physiol 2009;296:G910–22. [8] Hamadah IR, Banka N. Autosomal recessive plasma cell panniculitis with morphea-like clinical manifestation. J Am Acad Dermatol 2006;54:S189–91. [9] Marina S, Broshtilova V. POEMS in childhood. Pediatr Dermatol 2006;23:145–8. [10] Prendiville J, Rogers M, Kan A, de Castro F, Wong M, Junker A, et al. Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder? Pediatr Dermatol 2006;24:101–7.
a
Vered Molho-Pessacha,b Department of Dermatology, Hadassah-Hebrew University Medical Center, Israel b The Center for Genetic Diseases of the Skin and Hair, HadassahHebrew University Medical Center, Israel
Jose´ Suarez Department of Dermatology, Hospital Universitario Nuestra Sen˜ora de Candelaria Santa Cruz de Tenerife, Spain Christophe Perrin Department of Pathology, Nice University Hospital, Archet 2, Nice, France Christine Chiaverini Department of Dermatology, Nice University Hospital, Archet 2, Nice, France Victoria Doviner Department of Pathology, Hadassah-Hebrew University Medical Center, Israel Enriqueta Tristan-Clavijo Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocı´o/CSIC/Universidad de Sevilla, Sevilla, Spain Isabel Colmenero Department of Pathology, Hospital del Nin˜o Jesu´s, Madrid, Spain Fabienne Giuliano Department of Medical Genetics, Nice University Hospital, Archet 2, Nice, France Antonio Torrelo Servicio de Dermatologı´a, Hospital del Nin˜o Jesu´s, Madrid, Spain Abraham Zlotogorskia,b,* Department of Dermatology, Hadassah-Hebrew University Medical Center, Israel b The Center for Genetic Diseases of the Skin and Hair, HadassahHebrew University Medical Center, Israel
a
*Corresponding author at: Department of Dermatology, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91200, Israel. Tel.: +972 2 6777111; fax: +972 2 6432883 E-mail addresses: [email protected] (V. Molho-Pessach) [email protected] (A. Zlotogorski) [email protected] (J. Suarez) [email protected] (C. Perrin) [email protected] (C. Chiaverini) [email protected] (V. Doviner) [email protected] (E. Tristan-Clavijo) [email protected] (I. Colmenero) [email protected] (F. Giuliano) [email protected] (A. Torrelo) 26 June 2009 doi:10.1016/j.jdermsci.2009.09.011
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Hyoung-June Kim Kwang-Mi Kim Jae-Young Koh Min-Soo Noh Amore Pacific Corporation, 314-1 Boradong Giheung-gu, Yongin-si, Gyeonggi-do 449-729, Republic of Korea Mi-Kyung Park Hye-Ja Lee Soo-Youl Kim Chang-Hoon Lee* National Cancer Center, 809 Madu 1-dong, Goyang-si, Gyeonggi-do 416-769, Republic of Korea *Corresponding
author at: National Cancer Center, Molecular Oncology Branch, 809 Madu 1-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do, 416-769, Republic of Korea. Tel.: +82 31 920 2222/2232; fax: +82 31 920 2006 E-mail addresses: [email protected] [email protected] (C-H. Lee) 4 May 2009
doi:10.1016/j.jdermsci.2009.09.007
Letter to the Editor The H syndrome: Two novel mutations affecting the same amino acid residue of hENT3 H syndrome (OMIM 612391) is a recently described autosomalrecessive genodermatosis with systemic manifestations. The disease is characterized by the major clinical findings of progressive cutaneous hyperpigmentation and hypertrichosis located mainly over the lower limbs and lower abdomen, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height and hyperglycemia/diabetes mellitus [1,2]. The major histopathological findings include dermal infiltrate consisting mainly of histiocytes, later replaced by dermal and subcutaneous fibrosis [3]. Recently, we [2] and others [4] found that missense, nonsense, compound and deletion mutations in the SLC29A3 gene are responsible for this unique clinical picture. The SLC29A3 gene encodes the human equilibrative nucleoside transporter (hENT3), which mediates passive sodium-independent transport of nucleosides [5]. The exact cellular localization of hENT3, endosomal/lysosomal [6] or mitochondrial [7], and its function with relation to the H syndrome is still unclear. Here, we report two new cases of H syndrome, of Spanish and of Arab origin and describe two novel missense mutations. Patient 1 is a 13-year-old male, originating from a nonconsanguineous Spanish family (Fig. 1D). He first presented at the age of 4-year-old with an enlarging cutaneous mass over his left thigh with sclerodermoid induration and slight hyperpigmentation and hypertrichosis. Over the years the cutaneous changes gradually spread to involve the left shin, left lower abdomen and right thigh (Fig. 1A). Progressive bilateral sensorineural hearing loss presented when the patient was eight. At age 10 he developed diffuse alopecia of the scalp and halo nevi on the trunk. Additional significant findings on physical examination included gynecomastia (Fig. 1A), splenomegaly, scrotal masses, varicose veins and fixed flexion contractures of the proximal interphalangeal joint of his left fifth finger (Fig. 1A). Several weeks of prednisone treatment induced partial improvement of the thickened and indurated thigh masses and abdominal plaques.
Patient 2 is a 20-year-old male, originating from a consanguineous Arab family (Fig. 1D). He presented with hearing loss since age 4 and cutaneous induration and hyperpigmentation of the thighs which first appeared when he was 8-year-old and gradually extended to the genitals, back and lower limbs with overlying hypertrichosis. On physical examination, short stature (128 cm) and dysmorphic facies with downslanting palpebral fissures, short nose, anteverted nares and retrognathism were seen. Additional findings included arcus senilis, scrotal masses, hepatosplenomegaly and fixed flexion contractures of the proximal interphalangeal joints of the right fourth and fifth fingers and the left fifth finger. Informed consent for affected individuals and their family members was obtained and DNA was extracted from peripheral blood leukocytes using a commercial kit (Gentra System Inc., Minneapolis, MN). All SLC29A3 exons and splice junctions were PCR-amplified using intronic primers, as previously described [2]. PCR products were purified and sequenced on ABI 3700 capillary sequencer (Applied Biosystems, Foster City, CA). Important laboratory findings in both patients included mild microcytic anemia, elevated ESR and CRP, normal glucose level and liver function tests, and no paraprotein. Imaging (US/CT) demonstrated splenomegaly and/or hepatomegaly and lymphadenopathy. The major histological findings in skin biopsy included dermal infiltrate consisting of lymphocytes, plasma cells and CD68+ histiocytes, and dermal and subcutaneous fibrosis (Fig. 1B and C). In the Spanish patient a novel c.1087C>T missense mutation in exon 6 was found, changing arginine 363 to tryptophan (p.Arg363Trp) (Fig. 2A). In the Arab patient, another novel missense mutation, c.1088G>A, was found affecting the same amino acid residue as in patient 1, changing arginine 363 to glutamine (p.Arg363Gln) (Fig. 2A). These mutations were not detected in 100 Spanish and 102 Arab controls, respectively, suggesting this is not a common polymorphism. The clinical presentation and pathological findings of both patients are similar to the previously reported patients [1–4,8–10]. It is of interest that patient 1 had several unique clinical features: multiple halo nevi and diffuse scalp alopecia, consistent histolo-
60
Letters to the Editor / Journal of Dermatological Science 57 (2010) 57–73
Fig. 1. Pedigrees, clinical and histological findings in H syndrome patients. Clinical findings of patient 1 (A). (1) Extensive hyperpigmentation over lower abdomen, inguinal area and thighs. Scrotal masses are also noted. (2) Fixed flexion contracture of the proximal interphalangeal joint of the left fifth finger. (3) Prominent gynecomastia and dilated veins over abdominal wall. Histological findings of involved skin of left thigh in patient 1 showing dermal fibrosis extending to the subcutis (B), and an extensive histiocytic and dendritic infiltrate (C) (H&E stain, original magnifications 40, 200). (D) 1. Pedigree of patient 1. 2. Pedigree of patient 2. Affected male individuals are indicated in gray.
Fig. 2. (A) Sequence analysis of exon 6 of the SLC29A3 gene in patients 1 and 2: (top left to right) homozygous c.1087C>T mutation (patient 1), c.1088G>A (patient 2), and wild type. (Bottom) heterozygous state. (B) Evolutionary conservation of codon 363 in the SLC29A3 gene, coding in all species for arginine. Mutated nucleotide positions are shown by an arrow.
Letters to the Editor / Journal of Dermatological Science 57 (2010) 57–73
gically with alopecia areata, which were not previously reported in H syndrome, but may be incidental and unrelated to the disorder. It should also be noted that Cliffe et al. [4] described their patients as suffering from an allelic disorder to the H syndrome. Nevertheless, the clinical manifestations are identical. Distinguishing these disorders according to severity of flexion contractures, presence or absence of diabetes mellitus or deafness is artificial, and the differences in the clinical presentation are only due to phenotypic variability. Patients homozygous for the same mutation (e.g. G427S) may present with or without diabetes mellitus and/or deafness or any other feature characteristic of the H syndrome. Both novel mutations described in this report reside in the sixth exon of SLC29A3 and are located in a highly evolutionarily conserved position in the protein (Fig. 2B), between the eighth and ninth transmembranous domains of the transporter. Eight out of nine reported mutations were found in the sixth exon of the gene [2,4 and this report] indicating the importance of this coding region to the function of the transporter and the importance of initial screening of this exon for mutation’s detection in SLC29A3. The ENT family mediates the provision of nucleosides and nucleobases, derived from diet or produced by tissues for salvage pathways of nucleotide synthesis in cells deficient in de novo biosynthetic pathways. Nucleosides and nucleobases are converted in the cell by these salvage pathways to nucleotides which function in intermediary metabolism and as precursors for nucleic acid synthesis. By influencing adenosine concentration in the cell, ENTs also affect many physiological processes. It is not yet known why there are multiple nucleoside and nucleobase transporters with overlapping functions, but it is clear that hENT3 has an essential role in the normal function of multiple cell types and tissues uncompensated by other ENTs, as evident by the diverse clinical phenotype of H syndrome patients. In conclusion, two new patients with H syndrome are described, another patient of Arab origin, and the first of Spanish ancestry. Further recognition and awareness of the disorder will lead to the identification of more patients throughout the world. We anticipate that the study of these patients may better define the clinical spectrum of this unique syndrome, and will shed light on its pathogenesis. Acknowledgments We thank the family members for their participation in this study, and Sofia Babay for expert technical assistance. Funding sources: Authority for Research and Development, Hebrew University of Jerusalem (A.Z.), the Hadassah Medical Center physician scientist program and the Hadassah-Hebrew University Joint Research Fund (V.M.P.). References [1] Molho-Pessach V, Agha Z, Aamar S, Glaser B, Doviner V, Hiller N, et al. The H syndrome: a new genodermatosis characterized by indurated, hyperpigmented and hypertrichotic skin with systemic manifestations. J Am Acad Dermatol 2008;59:79–85. [2] Molho-Pessach V, Lerer I, Abeliovich D, Agha Z, Abu Libdeh A, Broshtilova V, et al. The H syndrome is caused by mutations in the nucleoside transporter hENT3. Am J Hum Genet 2008;83:529–34. [3] Doviner V, Maly A, Ne’eman, Z, Qawasmi R, Aamar S, Sultan M, et al. Syndrome: recently defined genodermatosis with distinct histologic features. A morphologic, histochemical, immunohistochemical and ultrastructural study of ten cases. Am J Dermatopathol; in press. [4] Cliffe ST, Kramer JM, Hussain K, Robben JH, de Jong EK, de Brouwer AP, et al. The SLC29A3 gene is mutated in pigmented hypertrichosis with insulin dependent diabetes mellitus syndrome and intersects with the insulin signaling pathway. Hum Mol Genet 2009;18:2257–65. [5] Hyde RJ, Cass CE, Young JD, Baldwin SA. The ENT family of eukaryote nucleoside and nucleobase transporters: Recent advances in the investigation of structure/function relationships and the identification of novel isoforms. Mol Membr Biol 2001;18:53–63.
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[6] Baldwin SA, Yao SY, Hyde RJ, Ng AML, Foppolo S, Barnes K, et al. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J Biol Chem 2005;280:15880–7. [7] Govindarajan R, Leung GP, Zhou M, Tse CM, Wang J, Unadkat JD. Facilitated mitochondrial import of anti-viral and anti-cancer nucleoside drugs by human equilibrative nucleoside transporter-3 (hENT3). Am J Physiol Gastrointest Liver Physiol 2009;296:G910–22. [8] Hamadah IR, Banka N. Autosomal recessive plasma cell panniculitis with morphea-like clinical manifestation. J Am Acad Dermatol 2006;54:S189–91. [9] Marina S, Broshtilova V. POEMS in childhood. Pediatr Dermatol 2006;23:145–8. [10] Prendiville J, Rogers M, Kan A, de Castro F, Wong M, Junker A, et al. Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder? Pediatr Dermatol 2006;24:101–7.
a
Vered Molho-Pessacha,b Department of Dermatology, Hadassah-Hebrew University Medical Center, Israel b The Center for Genetic Diseases of the Skin and Hair, HadassahHebrew University Medical Center, Israel
Jose´ Suarez Department of Dermatology, Hospital Universitario Nuestra Sen˜ora de Candelaria Santa Cruz de Tenerife, Spain Christophe Perrin Department of Pathology, Nice University Hospital, Archet 2, Nice, France Christine Chiaverini Department of Dermatology, Nice University Hospital, Archet 2, Nice, France Victoria Doviner Department of Pathology, Hadassah-Hebrew University Medical Center, Israel Enriqueta Tristan-Clavijo Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocı´o/CSIC/Universidad de Sevilla, Sevilla, Spain Isabel Colmenero Department of Pathology, Hospital del Nin˜o Jesu´s, Madrid, Spain Fabienne Giuliano Department of Medical Genetics, Nice University Hospital, Archet 2, Nice, France Antonio Torrelo Servicio de Dermatologı´a, Hospital del Nin˜o Jesu´s, Madrid, Spain Abraham Zlotogorskia,b,* Department of Dermatology, Hadassah-Hebrew University Medical Center, Israel b The Center for Genetic Diseases of the Skin and Hair, HadassahHebrew University Medical Center, Israel
a
*Corresponding author at: Department of Dermatology, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91200, Israel. Tel.: +972 2 6777111; fax: +972 2 6432883 E-mail addresses: [email protected] (V. Molho-Pessach) [email protected] (A. Zlotogorski) [email protected] (J. Suarez) [email protected] (C. Perrin) [email protected] (C. Chiaverini) [email protected] (V. Doviner) [email protected] (E. Tristan-Clavijo) [email protected] (I. Colmenero) [email protected] (F. Giuliano) [email protected] (A. Torrelo) 26 June 2009 doi:10.1016/j.jdermsci.2009.09.011