Glycerol kinase deficiency with neuromuscular, skeletal, and adrenal abnormalities

Guggenheim, Mary Anne; McCabe, Edward R.B.; Roig, Manuel G.; Goodman, Stephen I.; Lum, Gary; Bullen, William W.; Ringel, Steven P.

doi:10.1002/ana.410070509

Cited by 93 publications

(40 citation statements)

References 33 publications

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“…The patient, C.M., is the elder oftwo brothers with dystrophic myopathy, AHC, severe developmental delay, osteoporosis with pathological fractures, hyperglycerolemia, glyceroluria, and GKD (5)(6)(7)(8)11). The dystrophic myopathy shows the histological features ofearly DMD (7), but is clinically a mild form ofBecker muscular dystrophy (BMD) with absence of muscular pseudohypertrophy at 15 yr of age.…”

Section: Methodsmentioning

confidence: 99%

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Complementary DNA probes for the Duchenne muscular dystrophy locus demonstrate a previously undetectable deletion in a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia.

McCabe¹,

Towbin²,

Chamberlain³

et al. 1989

J. Clin. Invest.

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Genomic DNA from a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia was investigated using cDNA probes for the Duchenne muscular dystrophy (DMD) locus. Genomic probes had not detected a deletion in this patient. Southern analysis of Hind III-digested genomic DNA from this patient identified a deletion when the three distal Hinc II DMD cDNA fragments were used as probes. The deletion began in the genomic region corresponding to the 1.05-kb Hinc II cDNA fragment and extended through the 3' end of the DMD gene. This represents a centromeric breakpoint that corresponds to a position -10.2-10.6 kb from the 5' end of the 14-kb DMD cDNA. These investigations demonstrate the value of the DMD cDNA probes for improved diagnoses in patients with molecular lesions involving the DMD locus. Furthermore, this novel deletion involving the coding portion of the 3' end of the DMD gene assists in the ordering of exons in this region and will provide insight into the functional role of the carboxy terminus of the DMD gene product, dystrophin.

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Section: Methodsmentioning

confidence: 99%

“…Patients with this complex phenotype may have classical DMD or a milder dystrophic myopathy as seen in the original two brothers described with this disorder (6,7), the eldest of whom is the subject of these investigations. These patients also have developmental delay (3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Complementary DNA probes for the Duchenne muscular dystrophy locus demonstrate a previously undetectable deletion in a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia.

McCabe¹,

Towbin²,

Chamberlain³

et al. 1989

J. Clin. Invest.

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“…1979;Guggenheim et al. 1980;Bart ley et al, 1982;Petrykowski et al, 1982;Renier et al, 1983;Franeke.…”

Section: Discussionmentioning

confidence: 99%

Submicroscopic interstitial deletion of the X chromosome explains a complex genetic syndrome dominated by Norrie disease

Gal

Wieringa

Smeets

et al. 1986

Cytogenet Genome Res

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Norrie disease (ND), an X-linked recessive disorder, is characterized by congenital blindness followed by bulbar atrophy. We have examined a three-generation family in which ND is part of a complex X-linked syndrome with severe mental retardation, hypogonadism, growth disturbances, and increased susceptibility to infections as additional features. This syndrome is apparently due to an interstitial deletion, as evidenced by the failure of the L1.28 DNA probe (DXS7 locus, Xp11.3) to detect complementary DNA sequences on the defective X chromosome of an affected male and of several obligatory heterozygotes. Attempts to further define this deletion with other DNA probes from the proximal short arm of the X chromosome or by prometaphase chromosome analysis were unsuccessful.

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“…These robust, scale-free, hub and spoke networks are designed such that other nodes in the network can act as modifiers. One example of the phenotypic variability involves the original two brothers described with the contiguous gene syndrome including Becker muscular dystrophy, glycerol kinase deficiency, AHC and mental retardation (Guggenheim et al, 1980) who had complete deletion of DAX1. The younger brother died of AHC at 33 months and the older boy first presented with AHC at six years of age.…”

Section: Dax1 Mutations and Phenotypic Variabilitymentioning

confidence: 99%

DAX1: Increasing complexity in the roles of this novel nuclear receptor

McCabe

2007

Molecular and Cellular Endocrinology

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SummaryDAX1 (NR0B1) is a nuclear receptor with a characteristic C-terminal ligand binding domain, but an atypical DNA binding domain. Mutations in the DAX1 gene cause adrenal hypoplasia congenita (AHC) establishing its biological importance. Recent studies highlight the complexities of DAX1 regulation and function. There is considerable phenotypic variability in AHC suggesting the existence of DAX1 modifier genes and environmental influences on DAX1 function. The findings of an alternatively spliced DAX1A, more common than DAX1 in all tissues except testis, of DAX1 homodimers, and of DAX1 heterodimers with a number of transcription factor partners including DAX1A and SHP point to an expanded transcription regulatory network under DAX1 control. Model organisms (mice and zebrafish) are being used to identify other DAX1 functions and modifier genes to understand the pathogenesis of AHC and the lack of genotype-phenotype correlation. KeywordsDAX1; NR0B1; Adrenal hypoplasia congenital; DAX1A; DAX1 homodimerization; DAX1 modifier genes DAX1 and Adrenal Hypoplasia Congenita (AHC)Mutations in DAX1 (NR0B1), which is encoded in the Xp21 chromosomal region a, can lead to adrenal insufficiency with glucocorticoid and mineralocorticoid deficiency (McCabe, 2001). These mutations are responsible for many, but not all, patients with the cytomegalic form of adrenal hypoplasia congenita (AHC). These mutations also cause hypogonadotropic hypogonadism (HH) which is consistent with the expression of DAX1 in the hypothalamus and pituitary.Duplications of the region of the X chromosome containing DAX1 cause dosage sensitive sex reversal (Bardoni et al., 1994;McCabe, 2001). Transgenic XY mice with additional copies of the mouse DAX1 ortholog expressed at high levels do not have male to female sex reversal, but do show delayed testicular development (Swain et al., 1998). When these investigators crossed the transgenic female mice with poschiavinus males who have a weaker male sex determining Sry allele, they did observe complete sex reversal.

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Glycerol kinase deficiency with neuromuscular, skeletal, and adrenal abnormalities

Cited by 93 publications

References 33 publications

Complementary DNA probes for the Duchenne muscular dystrophy locus demonstrate a previously undetectable deletion in a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia.

Complementary DNA probes for the Duchenne muscular dystrophy locus demonstrate a previously undetectable deletion in a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia.

Submicroscopic interstitial deletion of the X chromosome explains a complex genetic syndrome dominated by Norrie disease

DAX1: Increasing complexity in the roles of this novel nuclear receptor

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