Smith‐Lemli‐Opitz syndrome in Japan

Tsukahara, Masato; Fujisawa, Kazuo; Yamamoto, Keiji; Hasui, Masaki; Saito, Chikako; Yamamaka, Tsutomu; Honda, Akira; Honda, Maki; Tint, G. Stephen; Salen, Gerald; Opitz, John M.

doi:10.1002/(sici)1096-8628(19980106)75:1<118::aid-ajmg24>3.3.co;2-3

Cited by 8 publications

(12 citation statements)

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“…For example, between 1995 and 1998, when knowledge of the biochemical defect was widespread, the two laboratories that perform at least 80% of biochemical testing for SLOS in the United States identified only about 40 new cases per year, or an estimated incidence of less than 1 in 60 000 births (Kelley and Tint, unpublished data). Similarly, estimates of only 1 in 60 000 newborns in the United Kingdom,27 1 in 80 000-100 000 births in The Netherlands (Waterham et al , unpublished data), and an even lower incidence in Japan36 have been reported. The number of cases with African,23 37Asian,38 39 or South American40 ancestry is also low.…”

Section: Clinical Overviewmentioning

confidence: 89%

The Smith-Lemli-Opitz syndrome

Kelley

Hennekam

2000

Journal of Medical Genetics

450

517

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The Smith-Lemli-Opitz syndrome (SLOS) is one of the archetypical multiple congenital malformation syndromes. The recent discovery of the biochemical cause of SLOS and the subsequent redefinition of SLOS as an inborn error of cholesterol metabolism have led to important new treatment possibilities for aVected patients. Moreover, the recent recognition of the important role of cholesterol in vertebrate embryogenesis, especially with regard to the hedgehog embryonic signalling pathway and its eVects on the expression of homeobox genes, has provided an explanation for the abnormal morphogenesis in the syndrome. The well known role of cholesterol in the formation of steroid hormones has also provided a possible explanation for the abnormal behavioural characteristics of SLOS. (J Med Genet 2000;37:321-335)

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Section: Clinical Overviewmentioning

confidence: 89%

The Smith-Lemli-Opitz syndrome

Kelley

Hennekam

2000

Journal of Medical Genetics

450

517

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“…The frequency of this syndrome in European populations was estimated between 1:15.000 to 1:40.000 Bzduch et al, 2000;Kelley and Hennekam, 2000]. There are ethnic groups with a lower incidence or no known case of SLOS like Africans, Chinese, and Japanese [Yu et al, 2000a;Tsukahara et al, 1998]. However, these frequency estimates are probably biased by several factors.…”

Section: Population Geneticsmentioning

confidence: 99%

Mutations in the human DHCR7 gene

Witsch‐Baumgartner¹,

Löffler²,

Utermann³

2001

Hum. Mutat.

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The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive metabolic disorder characterized by variable congenital malformations, facial dysmorphism, and mental retardation. Mutations in the DHCR7 gene have been identified in SLOS patients. This gene encodes for the enzyme Delta7-sterol reductase which catalyses the last step of cholesterol biosynthesis. Among the 73 different mutations observed so far, including 10 novel mutations reported in this review, the majority are missense mutations (65) which cluster in three domains of the protein: in the transmembrane domain (TM mutations), in the fourth cytoplasmic loop (4L mutations), and at the C-terminus (CT mutations). Two nonsense mutations, one splice site mutation, two single nucleotide insertions, and three deletions which likely all represent null mutations were also described. Expression studies have demonstrated a decreased protein stability for all analyzed missense mutations. By comparing clinical severity scores, biochemical data, and mutations in SLOS patients a genotype-phenotype correlation has been established. The null and 4L mutations are associated with a severe clinical phenotype, and TM and CT mutations are associated with a mild clinical phenotype. DHCR7 mutational spectra in SLOS patients of British, German, Italian, and Polish origin demonstrate significant geographic frequency differences of common DHCR7 mutations.

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“…Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomaly, autosomal recessive neurodevelopmental disorder caused by mutations in 7-dehydrocholesterol reductase (DHCR7) resulting in low levels of cholesterol and excess sterol precursors including 7-dehydrocholesterol (7-DHC) [Irons et al, 1993;Tint et al, 1994;Fitzky et al, 1998;Wassif et al, 1998;Waterham et al, 1998;Porter, 2000]. There is an estimated incidence of 1 in 10,000 to 60,000 live births, with a carrier frequency of about 0.8 to 2% [Tsukahara et al, 1998;Battaile et al, 2001;Nowaczyk et al, 2001;Wright et al, 2003]. Cholesterol is a biologic substrate for the formation of many important compounds such as myelin, cell membranes, bile acids, and steroid hormones.…”

Section: Introductionmentioning

confidence: 99%

Growth charts for individuals with Smith–Lemli–Opitz syndrome

Lee

McGready

Conley

et al. 2012

American J of Med Genetics Pt A

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Smith-Lemli-Opitz syndrome (SLOS) is a rare multiple congenital anomaly neurodevelopmental syndrome of impaired cholesterol synthesis. Growth restriction and developmental delay are very common clinical manifestations of SLOS. The degree, etiology, and consequences of growth restriction in SLOS remain an area of limited knowledge to the scientific community. There have been no studies describing the growth parameters and providing reference growth charts for individuals with SLOS. Our longitudinal data from 78 patients between the ages of 0.1 and 16 years with SLOS shows a growth restriction of about 2 standard deviations below the Centers for Disease Control (CDC) norms for age. This study represents comprehensive anthropometric data from the largest cohort available, and proposes growth charts for widespread use in the management and study of individuals with SLOS.

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Smith‐Lemli‐Opitz syndrome in Japan

Cited by 8 publications

References 0 publications

The Smith-Lemli-Opitz syndrome

The Smith-Lemli-Opitz syndrome

Mutations in the human DHCR7 gene

Growth charts for individuals with Smith–Lemli–Opitz syndrome

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