Compound heterozygous SLC29A3 mutation causes H syndrome in a Moroccan patient: A case report

Bakhchane, Amina; Kindil, Zineb; Charoute, Hicham; Benchikhi, K.; Khadir, K.; Nadifi, Sellama; Baline, K.; Roky, Rachida; Barakat, Abdelhamid

doi:10.1016/j.retram.2016.01.008

Cited by 10 publications

(5 citation statements)

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“…Patients 4 and 5 are heterozygous for the c.1309G > A (p.G437R) mutation, one of the most common mutations found in patients of Arab descent [ 26 ]. The other mutation in patients 4 and 5 results in a splice site mutation at c.300 due to a G > C substitution, which has been recently described in a Moroccan patient [ 27 ]. Of interest, a different mutation at this same site (c.300 G > A) has been reported in patients of Pakistani descent with Faisalbad histiocytosis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

H syndrome: 5 new cases from the United States with novel features and responses to therapy

et al. 2017

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BackgroundH Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). Less than 100 patients with H syndrome have been described in the literature, with the majority being of Arab descent, and only a few from North America.Case presentationHere we report five pediatric patients from three medical centers in the United States who were identified to have H syndrome by whole exome sequencing. These five patients, all of whom presented to pediatric rheumatologists prior to diagnosis, include two of Northern European descent, bringing the total number of Caucasian patients described to three. The patients share many of the characteristics previously reported with H syndrome, including hyperpigmentation, hypertrichosis, short stature, insulin-dependent diabetes, arthritis and systemic inflammation, as well as some novel features, including selective IgG subclass deficiency and autoimmune hepatitis. They share genetic mutations previously described in patients of the same ethnic background, as well as a novel mutation. In two patients, treatment with prednisone improved inflammation, however both patients flared once prednisone was tapered. In one of these patients, treatment with tocilizumab alone resulted in marked improvement in systemic inflammation and growth. The other had partial response to prednisone, azathioprine, and TNF inhibition; thus, his anti-TNF biologic was recently switched to tocilizumab due to persistent polyarthritis. Another patient improved on Methotrexate, with further improvement after the addition of tocilizumab.ConclusionH syndrome is a rare autoinflammatory syndrome with pleiotropic manifestations that affect multiple organ systems and is often mistaken for other conditions. Rheumatologists should be aware of this syndrome and its association with arthritis. It should be considered in patients with short stature and systemic inflammation, particularly with cutaneous findings. Some patients respond to treatment with biologics alone or in combination with other immune suppressants; in particular, treatment of systemic inflammation with IL-6 blockade appears to be promising. Overall, better identification and understanding of the pathophysiology may help devise earlier diagnosis and better treatment strategies.

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Section: Discussionmentioning

confidence: 99%

H syndrome: 5 new cases from the United States with novel features and responses to therapy

et al. 2017

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“…Since 2014, 17 patients have been reported. 11,20,[23][24][25][26][27][28][29][30] Molho-Pessach et al 5 emphasized that the finding of several different mutations in a small geographic region implies that H syndrome may be rather common and underdiagnosed owing to the fact that many patients have a very mild clinical presentation. In our context, geographic endogamy is frequent in Tunisia, especially in rural areas where it could reach 90% and familial endogamy or interrelated marriages are profoundly rooted with an estimated rate of 30% of all kind of unions.…”

Section: Discussionmentioning

confidence: 99%

H syndrome: Clinical, histological and genetic investigation in Tunisian patients

Jaouadi

Zaouak

Sellami

et al. 2018

The Journal of Dermatology

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H syndrome is a rare autosomal recessive disorder with characteristic dermatological findings consisting of hyperpigmentation and hypertrichosis patches mainly located on the inner thighs and multisystemic involvement including hepatosplenomegaly, hearing loss, heart abnormalities and hypogonadism. The aim of this study was to conduct a clinical and genetic investigation in five unrelated Tunisian patients with suspected H syndrome. Hence, genetic analysis of the SLC29A3 gene was performed for four patients with a clinical diagnosis of H syndrome. We identified a novel frame-shift mutation in the SLC29A3 gene in a female patient with a severe clinical presentation. Furthermore, we report two mutations previously described, the p.R363Q mutation in a male patient and the p.P324L mutation in two patients of different age and sex. This paper extends the mutation spectrum of H syndrome by reporting a novel frame-shift mutation, the p.S15Pfs*86 in exon 2 of SLC29A3 gene and emphasizes the relevance of genetic testing for its considerable implications in early diagnosis and clinical management.

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“…In further support of this disease etiology, human ENT3 has been shown to play roles in bone physiology, immune function, macrophage homeostasis, and T-cell survival, through maintenance of organellar integrity and function. Although some mutations of slc29a3 that lead to such disorders are nonsense or frameshift, , many are missense that diminish transporter stability, localization, and transport activity . Further, many of these mutations map to conserved positions of potential structural and functional importance in the recently determined human ENT1 crystal structure (to be discussed later in this review).…”

Section: Equilibrative Nucleoside Transportersmentioning

confidence: 99%

Toward a Molecular Basis of Cellular Nucleoside Transport in Humans

Wright

Lee

2020

Chem. Rev.

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Nucleosides play central roles in all facets of life, from metabolism to cellular signaling. Because of their physiochemical properties, nucleosides are lipid bilayer impermeable and thus rely on dedicated transport systems to cross biological membranes. In humans, two unrelated protein families mediate nucleoside membrane transport: the concentrative and equilibrative nucleoside transporter families. The objective of this review is to provide a broad outlook on the current status of nucleoside transport research. We will discuss the role played by nucleoside transporters in human health and disease, with emphasis placed on recent structural advancements that have revealed detailed molecular principles of these important cellular transport systems and exploitable pharmacological features.

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Compound heterozygous SLC29A3 mutation causes H syndrome in a Moroccan patient: A case report

Cited by 10 publications

References 13 publications

H syndrome: 5 new cases from the United States with novel features and responses to therapy

H syndrome: 5 new cases from the United States with novel features and responses to therapy

H syndrome: Clinical, histological and genetic investigation in Tunisian patients

Toward a Molecular Basis of Cellular Nucleoside Transport in Humans

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