Characterization of a new X‐linked mental retardation syndrome with microcephaly, cortical malformation, and thin habitus

Souich, Christèle du; Chou, Athena; Yin, Jingyi; Oh, Tracey; Nelson, Tanya N.; Hurlburt, Jane; Arbour, Laura; Friedlander, Robin; McGillivray, Barbara; Tyshchenko, Nataliya; Rump, Andreas; Poskitt, Kenneth J.; Demos, Michelle; Allen, Margot I. Van; Boerkoel, Cornelius F.

doi:10.1002/ajmg.a.33071

Cited by 28 publications

(37 citation statements)

References 37 publications

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“…Affected males demonstrate mild to severe mental retardation, microcephaly, CNS malformations, seizures, dysmorphic facies, and no features of CHILD Syndrome. The disorder has been given the eponym of CK syndrome ( 302 ). The fi rst family of two brothers was reported among 208 males with X-linked mental retardation; they had an insertion and frameshift mutation near the C terminus of NSDHL that disrupted the ER localization signal of the protein ( 301 ).…”

Section: Additional Phenotypes Associated With Genes Of the C-4 Steromentioning

confidence: 99%

Malformation syndromes caused by disorders of cholesterol synthesis

Porter

Herman

2011

Journal of Lipid Research

407

440

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Section: Additional Phenotypes Associated With Genes Of the C-4 Steromentioning

confidence: 99%

Malformation syndromes caused by disorders of cholesterol synthesis

Porter

Herman

2011

Journal of Lipid Research

407

440

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“…As observed for expression of human NSDHL encoded mRNA, mouse Nsdhl mRNA was expressed in all tissues affected in CHILD and CK syndromes as well as in tissues unaffected by these disorders (Supplementary Fig. 3) (du Souich et al 2009(du Souich et al , 2011McLarren et al 2010;Cunningham et al 2009;Liu et al 1999). The mouse Nsdhl in situ hybridization showed five patterns of temporal expression (Supplementary Fig.…”

Section: Hematopoietic Tissuesmentioning

confidence: 63%

“…Individuals with CHILD syndrome have punctate calcifications of cartilaginous structures, bony deficiencies of the affected limbs, scoliosis, and kyphosis (du Souich et al 2011). Individuals with CK syndrome have micrognathia, a high arched palate, scoliosis, kyphosis, short stature and relatively long digits and limbs(du Souich et al 2009;McLarren et al 2010). Proximal tibial growth plate chondrocytes in the zone of hypertrophy strongly expressed NSDHL.…”

mentioning

confidence: 99%

Expression profile of NSDHL in human peripheral tissues

et al. 2011

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NAD(P) steroid dehydrogenase-like (NSDHL) is an X-linked gene that encodes a 3β-hydroxysteroid dehydrogenase in the cholesterol biosynthetic pathway. Loss-of-function mutations in NSDHL cause Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects (CHILD) and CK syndromes. CHILD syndrome is a male lethal X-linked dominant disorder characterized by asymmetric skin and limb anomalies in affected females. CK syndrome is an intellectual disability disorder characterized by disproportionate short stature, brain malformations, and dysmorphic features in affected males. To understand better the relationship of the expression of mRNA and protein encoded by human NSDHL to the peripheral malformations of these disorders, we characterized the peripheral expression of the mRNA and protein by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), immunoblotting and immunohistochemistry. We also profiled the mRNA expression of mouse Nsdhl by in situ hybridization. Expression of the mRNA and protein encoded by human NSDHL parallels that of mouse Nsdhl mRNA for most but not all tissues. Furthermore, human NSDHL protein and mouse Nsdhl mRNA were expressed in tissues synthesizing cholesterol and steroids and in all peripheral tissues affected by CHILD or CK syndromes.

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“…Of the 195 genes located in this interval, there is one gene involved in the cholesterol synthesis pathway, sterol-4-alpha-carboxylate 3-dehydrogenase ( Nsdhl ). Mutations in NSDHL are associated with the very rare CHILD syndrome in humans, which is an X-linked dominant disorder of lipid metabolism (Konig et al 2000; Bornholdt et al 2005), as well as the recently described CK syndrome (du Souich et al 2009; McLarren et al 2010). Because of the known relationship between NSDHL and lipid metabolism, the coding region of Nsdhl was sequenced for both I/L and KK strains (Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

Identification of a Novel Polymorphism in X-Linked Sterol-4-Alpha-Carboxylate 3-Dehydrogenase (Nsdhl) Associated with Reduced High-Density Lipoprotein Cholesterol Levels in I/LnJ Mice

Bautz

Broman

Threadgill

2013

G3 Genes|Genomes|Genetics

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Loci controlling plasma lipid concentrations were identified by performing a quantitative trait locus analysis on genotypes from 233 mice from a F2 cross between KK/HlJ and I/LnJ, two strains known to differ in their high-density lipoprotein (HDL) cholesterol levels. When fed a standard diet, HDL cholesterol concentration was affected by two significant loci, the Apoa2 locus on Chromosome (Chr) 1 and a novel locus on Chr X, along with one suggestive locus on Chr 6. Non-HDL concentration also was affected by loci on Chr 1 and X along with a suggestive locus on Chr 3. Additional loci that may be sex-specific were identified for HDL cholesterol on Chr 2, 3, and 4 and for non-HDL cholesterol on Chr 5, 7, and 14. Further investigation into the potential causative gene on Chr X for reduced HDL cholesterol levels revealed a novel, I/LnJ-specific nonsynonymous polymorphism in Nsdhl, which codes for sterol-4-alpha-carboxylate 3-dehydrogenase in the cholesterol synthesis pathway. Although many lipid quantitative trait locus have been reported previously, these data suggest there are additional genes left to be identified that control lipid levels and that can provide new pharmaceutical targets.

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Characterization of a new X‐linked mental retardation syndrome with microcephaly, cortical malformation, and thin habitus

Cited by 28 publications

References 37 publications

Malformation syndromes caused by disorders of cholesterol synthesis

Malformation syndromes caused by disorders of cholesterol synthesis

Expression profile of NSDHL in human peripheral tissues

Identification of a Novel Polymorphism in X-Linked Sterol-4-Alpha-Carboxylate 3-Dehydrogenase (Nsdhl) Associated with Reduced High-Density Lipoprotein Cholesterol Levels in I/LnJ Mice

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