The H Syndrome: Molecular Diagnosis Using Next-Generation Sequencing

Mruthyunjaya, Mahesh Doddabelavangala; Chapla, Aaron; Shetty, Sahana; Shyamasunder, Asha Hesarghatta; Mathew, Lydia; George, Renu; Paul, Thomas; Nicolaï, Thomas

doi:10.4158/ep15762.cr

Cited by 9 publications

(13 citation statements)

References 11 publications

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“…The condition is caused by a mutation in the solute carrier family 29 (nucleoside transporters), member 3 (SLC29A3) gene, which encodes for the hENT3 [ 4 , 7 ]. hENT3 is a nucleoside transporter that functions in transporting nucleosides through a passive sodium-independent process, a crucial step for nucleotide synthesis via salvage pathway [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

H Syndrome: Report of The First Case in African Ethnicity

Elmansour¹,

Babikir²

2022

Cureus

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H syndrome is an autosomal recessive multisystemic disease with a very low prevalence rate, characterized by indurated cutaneous hyperpigmentation, hypertrichosis, and various systemic manifestations. The syndrome is caused by mutations in SLC29A3 gene on chromosome 10q23, encoding for human equilibrative transporter 3 (hENT3). So far, only 100-120 patients with H syndrome have been described in the literature, with predominance among Indian, North-American, and Arab ethnicities. This case report describes the first one of H-syndrome rarities in African ethnicity, a 30-year-old Sudanese male misdiagnosed with rheumatoid arthritis. The patient exhibited more than 90% of the clinical characteristics of H syndrome including obesity, short stature, characteristic hyperpigmented, sclerotic cutaneous plaques with induration and hypertrichosis, inflammatory arthropathy, hallux valgus, flexion deformity of toes, exophthalmos, cardiac anomaly, hypogonadism, and splenomegaly and characteristic histologic findings of dermal fibrosis, histiocytosis, lymphoid aggregation, and vascular proliferation. H syndrome is an extremely rare autoinflammatory condition that has a complex constellation of pleiotropic manifestations with multisystemic involvement. And while further identification and better pathophysiological understanding of H syndrome are needed, physicians worldwide should be vigilant about the overlapping features of H syndrome with many other rheumatological, cutaneous, and genetic diseases.

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Section: Discussionmentioning

confidence: 99%

H Syndrome: Report of The First Case in African Ethnicity

Elmansour¹,

Babikir²

2022

Cureus

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“…The PHID syndrome is an allelic variant of the H syndrome which is a cluster of disorders characterized by cutaneous hyperpigmentation, hearing impairment, heart abnormalities, hypertrichosis, hepatomegaly, hypogonadism, and histiocytosis . Additional features of the H syndrome can include short stature, hallux valgus, fixed flexion contractions of the proximal interphalangeal, and toe joints in addition to lymphadenopathy . The characteristic phenotype of this disease cluster is the cutaneous hyperpigmented, hypertrichotic, and indurated patches that appear between the first and second decades of life .…”

Section: Introductionmentioning

confidence: 99%

“…Additional features of the H syndrome can include short stature, hallux valgus, fixed flexion contractions of the proximal interphalangeal, and toe joints in addition to lymphadenopathy . The characteristic phenotype of this disease cluster is the cutaneous hyperpigmented, hypertrichotic, and indurated patches that appear between the first and second decades of life . These pigmented plaques are histopathologically characterized by inflammation, excessive histiocytes, acanthosis in the basal layer of the skin, and by the presence of excessive plasma cells in the dermis and subcutis …”

Section: Introductionmentioning

confidence: 99%

“…hypertrichotic, and indurated patches that appear between the first and second decades of life. 6 These pigmented plaques are histopathologically characterized by inflammation, excessive histiocytes, acanthosis in the basal layer of the skin, and by the presence of excessive plasma cells in the dermis and subcutis. 3,7 The overlapping features of the PHID and H syndromes include the hyperpigmented lesions and plaques particularly on the inner thighs, shins, genitals and abdomen, general hypertrichosis, perivascular lymphohistiocytosis, and mild to moderate lymphadenopathy.…”

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confidence: 99%

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A novel 3′ untranslated region mutation in theSLC29A3gene associated with pigmentary hypertrichosis and non‐autoimmune insulin‐dependent diabetes mellitus syndrome

Riachi¹,

Baş

Darendelıler

et al. 2019

Pediatr Diabetes

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Background Pigmentary hypertrichosis and non‐autoimmune insulin‐dependent diabetes mellitus (PHID) is one of the rare H syndrome diseases mainly characterized by hyperpigmentation, hypertrichosis, sensorineural hearing loss, cardiac complications, developmental delay, and diabetes mellitus (DM). Mutations in the coding regions of the SLC29A3 gene that encodes for an equilibrative nucleoside transporter (ENT3) have been reported to cause the phenotypic spectrum of the H syndrome. Disease‐causing mutations in the untranslated regions (UTRs) of the SLC29A3 gene have not been previously described in the literature. The aim of the study is to describe and assess the pathogenicity of a novel 3’UTR mutation in the SLC29A3 gene associated with the PHID phenotype in two Turkish patients. Methods The mutation was identified by a targeted gene approach. To understand the pathogenicity of this 3’UTR mutation, RNA and protein expression studies were performed by using the quantitative real‐time polymerase chain reaction method and western blotting, respectively, using fibroblasts cultured from the patients' skin biopsies. Results SLC29A3 and ENT3 expression levels were both decreased in the patients compared to controls matched for passage numbers, RNA, and protein extraction methods. Conclusions A novel 3’UTR mutation in the SLC29A3 gene is associated with the PHID syndrome, highlighting a potentially new pathological mechanism for this disease. The involvement of the 3’UTR has not been previously established in any of the H syndrome disease cluster or in any complex syndrome of DM.

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“…By using this approach, a homozygous missense mutation (c.400C>T, p.Arg134Cys) was identified in the SLC29A3 gene in this patient. This is the first report utilizing NGS technologies for rapid and inexpensive molecular diagnosis of H syndrome (3). See accompanying article, p. e65.…”

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confidence: 99%