Compound heterozygous splice site variants in the SCLT1 gene highlight an additional candidate locus for Senior-Løken syndrome

Katagiri, Satoshi; Hayashi, Takaaki; Yoshitake, Kazutoshi; Murai, Noriyuki; Matsui, Zenichi; Kubo, Hiroyuki; Satoh, Hiroyuki; Matsufuji, Senya; Takamura, Tsuyoshi; Yokoo, Takashi; Omori, Yoshihiro; Furukawa, Takahisa; Iwata, Takeshi; Nakano, Tadashi

doi:10.1038/s41598-018-35152-6

Cited by 11 publications

(16 citation statements)

References 37 publications

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“…In addition, she showed mild intellectual disability and obesity, but no polydactyly was observed. The clinical manifestations of our patients and those of the patient reported by Katagiri et al [6] are similar. Polydactyly is seen in most patients with BBS, except in patients with BBS due to SDCCAG8 aberrations.…”

Section: Discussionsupporting

confidence: 88%

“…3). This exon skipping was the same as that in the case of the patient reported by Katagiri et al [6]. The c.1631A > G mutation was registered in dbSNP as rs762215370 and its allele frequency in the Japanese population was reported to be 0.12%.…”

Section: Discussionsupporting

confidence: 86%

“…Renal diseases are common in BBS patients. Katagiri et al reported that the patient showed severe renal disorder during childhood [6]. The patient reported by Adly et al died at the age of 3 months; therefore, details regarding renal diseases of this patient are unknown [5].…”

Section: Discussionmentioning

confidence: 82%

“…The first patient with SCLT1 aberration reported by Adly et al [5] presented a severe midline cleft lip, microcephaly, bilateral coloboma, abnormal genitalia, and congenital heart disease, but polydactyly was not observed; he was diagnosed with OFD9. A Japanese girl reported by Katagiri et al [6] showed RP and NPHP, resulting in the diagnosis of SLSN. In addition, she showed mild intellectual disability and obesity, but no polydactyly was observed.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the sodium channel and clathrin linker 1 gene (SCLT1, 4q28.2) has been reported to be the causative gene for oral-facial-digital syndrome type IX (OFD9) [5], and Senior-Løken syndrome (SLSN) [6]. SCLT1 encodes an adaptor protein associated with the sodium voltage-gated channel alpha subunit 10 and clathrin [7], and SCLT1 was identified as one of the component proteins of the distal appendages of centrioles, which was proposed to anchor cilia to the plasma membrane [8].…”

Section: Introductionmentioning

confidence: 99%

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Bardet–Biedl syndrome in two unrelated patients with identical compound heterozygous SCLT1 mutations

et al. 2020

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Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by retinitis pigmentosa (RP), truncal obesity, cognitive impairment, hypogonadism in men, polydactyly, and renal abnormalities with severe renal dysfunction. Twenty-two causative genes have already been reported for this disorder. In this study, we identified two unrelated Japanese patients with clinical diagnoses of BBS associated with compound heterozygous SCLT1 mutation. Patient 1 was a 10-year-old girl, and patient 2 was a 22-year-old man. Both the patients showed severe renal dysfunction in childhood, RP, mild intellectual disability, short stature, and truncal obesity, without oral aberrations and polydactyly. Patient 2 also had hypogonadism. We identified two missense variants in SCLT1, c.[1218G > A] and [1631A > G], in both the patients by next-generation sequencing. Subsequent cDNA analysis revealed that c.1218G > A affected exon 14 skipping in SCLT1. To date, SCLT1 has been reported as the causative gene of oral-facial-digital syndrome type IX, and Senior-Løken syndrome. The phenotypes of both the present patients were compatible with BBS. These results highlight SCLT1 as an additional candidate for BBS phenotype in an autosomal recessive manner.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bardet–Biedl syndrome in two unrelated patients with identical compound heterozygous SCLT1 mutations

et al. 2020

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Genome sequencing identifies biallelic variants in SCLT1 in a patient with syndromic nephronophthisis: Reflections on the SCLT1‐related ciliopathy spectrum

Gillesse,

Wade,

Parboosingh

et al. 2024

American J of Med Genetics Pt A

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Ciliopathies represent a major category of rare multisystem disease. Arriving at a specific diagnosis for a given patient is challenged by the significant genetic and clinical heterogeneity of these conditions. We report the outcome of the diagnostic odyssey of a child with obesity, renal, and retinal disease. Genome sequencing identified biallelic splice site variants in sodium channel and clathrin linker 1 (SCLT1), an emerging ciliopathy gene. We review the literature on all patients reported with biallelic SCLT1 variants highlighting a frequent clinical presentation that overlaps Bardet–Biedl and Senior–Loken syndromes. We also discuss current concepts in syndrome designation in light of these data.

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Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings

Mizobuchi

Hayashi

Yoshitake

et al. 2020

Molec Gen & Gen Med

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Background Biallelic CLN3 gene variants have been found in either juvenile‐onset neuronal ceroid lipofuscinosis (JNCL) or isolated retinal dystrophy. It has been reported that most JNCL patients carry a common 1.02‐kb deletion variant homozygously. Clinical characteristics of patients with biallelic CLN3 missense variants are not well elucidated. Methods We described a 26‐year‐old Japanese male patient with isolated retinal dystrophy. Whole‐exome sequencing (WES) and transmission electron microscopy (TEM) were performed. Results Whole‐exome sequencing identified a novel homozygous CLN3 missense variant [c.482C>T; p.(Ser161Leu)]. Ophthalmoscopy revealed retinal degeneration and macular atrophy, and later attenuated retinal vessels. Severely reduced responses were observed in both rod and cone electroretinograms. In TEM of the patient's lymphocytes, fingerprint profiles, which are specific findings in CLN3 ‐associated JNCL, were observed in 16/624 (2.56%) lymphocytes of the patient, who has never exhibited neurological signs during the 13‐year follow‐up period. Conclusion Our results indicated that this novel CLN3 missense variant is associated with teenage‐onset isolated retinal dystrophy. This is the first report of any patient with CLN3 ‐associated disorder in the Japanese population. Although fingerprint profiles have never been reported in CLN3 ‐associated isolated retinal dystrophy, these profiles were observed, albeit infrequently, suggesting that frequency of the fingerprint profiles might depend on variant types.

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Compound heterozygous splice site variants in the SCLT1 gene highlight an additional candidate locus for Senior-Løken syndrome

Cited by 11 publications

References 37 publications

Bardet–Biedl syndrome in two unrelated patients with identical compound heterozygous SCLT1 mutations

Bardet–Biedl syndrome in two unrelated patients with identical compound heterozygous SCLT1 mutations

Genome sequencing identifies biallelic variants in SCLT1 in a patient with syndromic nephronophthisis: Reflections on the SCLT1‐related ciliopathy spectrum

Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings

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