Molecular analysis and long‐term clinical evaluation of three siblings with Alström syndrome

Ozgul, RK; Satman, İlhan; Collin, GB; Hinman, E. Harold; Marshall, J.D.; Kocaman, Orhan; Tütüncü, Yıldız; Yılmaz, Temel; Naggert, Juergen K

doi:10.1111/j.1399-0004.2007.00848.x

Cited by 19 publications

(10 citation statements)

References 14 publications

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“…Eight novel and 12 previously reported 12, 16, 23, 27, 28, 31, 37 mutations were identified in exons 8, 10, 11, 16 and intron 18 in 25 kindreds (Table 1 and 2). …”

Section: Resultsmentioning

confidence: 97%

The phenotypic and molecular genetic spectrum of Alström syndrome in 44 Turkish kindreds and a literature review of Alström syndrome in Turkey

et al. 2014

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Alström Syndrome is an autosomal recessive disease characterized by multiple organ involvement, including neurosensory vision and hearing loss, childhood obesity, diabetes mellitus, cardiomyopathy, hypogonadism, and pulmonary, hepatic, renal failure, and systemic fibrosis. Alström Syndrome is caused by mutations in ALMS1, and ALMS1 protein is thought to play a role in microtubule organization, intraflagellar transport, endosome recycling and cell cycle regulation. Here, we report extensive phenotypic and genetic analysis of a large cohort of Turkish patients with Alström Syndrome. We evaluated 61 Turkish patients, including 11 previously reported, for both clinical spectrum and mutations in ALMS1. To reveal the molecular diagnosis of the patients, there different approaches were used in combination, a cohort of patients were screened by the gene array to detect the common mutations in ALMS1 gene, then in patients having any of common ALMS1 mutations were subjected to direct DNA sequencing or next generation sequencing for the screening of mutations in all coding regions of the gene. In total, 20 distinct disease-causing nucleotide changes in ALMS1 have been identified, 8 of which are novel, thereby increasing the reported ALMS1 mutations by 6% (8/120). Five disease-causing variants were identified in more than one kindred, but most alleles were unique to each single patient and identified only once (16/20). So far, 16 mutations identified were specific to the Turkish population, and four have also been reported in other ethnicities. Additionally, 49 variants of uncertain pathogenicity were noted, and four of these were very rare and probably or likely deleterious according to in silico mutation prediction analyses. Alström Syndrome has a relatively high incidence in Turkey and the present study shows that the ALMS1 mutations are largely heterogeneous; thus, these data from a particular population may provide a unique source for the identification of additional mutations underlying Alström Syndrome and contribute to genotype-phenotype correlation studies.

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“…Eight novel and 12 previously reported 12, 16, 23, 27, 28, 31, 37 mutations were identified in exons 8, 10, 11, 16 and intron 18 in 25 kindreds (Table 1 and 2). …”

Section: Resultsmentioning

confidence: 97%

The phenotypic and molecular genetic spectrum of Alström syndrome in 44 Turkish kindreds and a literature review of Alström syndrome in Turkey

et al. 2014

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show abstract

“…Both mutations were previously described as being pathogenic. The c.8164C>T mutation was reported in three siblings of a Turkish family with AS, all with pigmentary retinopathy 2. The affected individuals were homozygous for this mutation.…”

Section: Investigationsmentioning

confidence: 88%

Alstrom syndrome - an uncommon cause of early childhood retinal dystrophy

Sheck

Al-Taie²,

Sharp³

et al. 2011

Case Reports

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“…Hypothyroidism A hypothyroid condition, mostly primary (low free thyroxine (FT4), high thyroidstimulating hormone (TSH)), is observed in approximately 20% of patients [Michaud et al, 1996]. Subclinical hypothyroidisms in about 30% of patients and isolated incidents of hyperthyroidism have been observed [Ozgül et al, 2007]. The mechanism of the hypothyroidism remains unknown, although it could be hypothesized that fibrotic infiltrations in the thyroid gland play a role.…”

Section: Minor Featuresmentioning

confidence: 99%

“…A subset of patients have developed more severe complications such as marked frequency and urgency, incontinence, and significant perineal or abdominal pain requiring surgical intervention [Charles et al, 1990, 2007a. Anatomical abnormalities can also occur in ALMS, including calyceal deformities, narrowed ureteropelvic angles, dilated ureters, and misalignment of the kidneys [Ozgül et al, 2007].…”

Section: Urological Dysfunctionmentioning

confidence: 99%

“…A major problem in arriving at a diagnosis of ALMS is the high phenotypic heterogeneity that can occur even within the same affected family [Ozgül et al, 2007, Hoffman et al, 2005& Titomanilo et al, 2004. Marshall and co-workers [Marshall et al, 2007a] provided a comprehensive guidance for diagnostic criteria in their 2007 publication, as summarized below:…”

Section: Diagnostic Criteria In Alström Syndromementioning

confidence: 99%

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