Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lowe oculocerebrorenal syndrome (OCRL) (MIM 309000) is a rare X-linked multisystem disorder characterized by congenital cataracts, muscular hypotonia, areflexia, mental retardation, maladaptive behavior, renal tubular dysfunction, vitamin-D-resistant rickets, and scoliosis. The underlying gene OCRL1 is located on chromosome Xq25-q26 and contains 24 exons. It encodes a 105-kDa phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P(2)) 5-phosphatase that is localized to the Golgi complex. To confirm the clinical diagnosis and to assess the carrier state of female relatives for genetic counseling we examined 6 independent patients and their families (a total of 23 individuals) using an improved mutation screening strategy for the OCRL1 gene by sequencing of large PCR amplicons. Four novel and two known mutations were identified: three premature terminations caused by either frameshift mutations (1899insT in exon 17 and 2104-2105delGT in exon 18) or a nonsense mutation (1399C > T in exon 12), two missense mutations (1676G > A and 1754C > T in exon 15), and a 6-bp deletion (1609-1614delAAGTAT in exon 14). An ophthalmological examination was performed in all patients and 14 female relatives. All genotypically proven carrier females showed characteristic lenticular opacities, while all proven noncarriers were lacking this phenotypic finding. The results confirm that ophthalmological evaluation is an apparently reliable first-line method to ascertain the carrier state in Lowe oculocerebrorenal syndrome. The high expressivity of lenticular symptoms in OCRL1 gene carriers is consistent with the hypothesis that (PtdIns[4,5]P(2)) 5-phosphatase activity has low functional reserve capacity for maintaining a balanced homeostasis of lenticular metabolism.
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PMID:Carrier assessment in families with lowe oculocerebrorenal syndrome: novel mutations in the OCRL1 gene and correlation of direct DNA diagnosis with ocular examination. 1076 76

Lowe syndrome (the oculocerebrorenal syndrome of Lowe, OCRL) is a multisystem disorder characterised by anomalies affecting the eye, the nervous system and the kidney. It is a uncommon, panethnic, X-linked disease, with estimated prevalence in the general population of approximately 1 in 500,000. Bilateral cataract and severe hypotonia are present at birth. In the subsequent weeks or months, a proximal renal tubulopathy (Fanconi-type) becomes evident and the ocular picture may be complicated by glaucoma and cheloids. Psychomotor retardation is evident in childhood, while behavioural problems prevail and renal complications arise in adolescence. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate 5 phosphatase, PtdIns (4,5)P2, in the trans-Golgi network is responsible for the disease. Both enzymatic and molecular testing are available for confirmation of the diagnosis and for prenatal detection of the disease. The treatment includes: cataract extraction, glaucoma control, physical and speech therapy, use of drugs to address behavioural problems, and correction of the tubular acidosis and the bone disease with the use of bicarbonate, phosphate, potassium and water. Life span rarely exceeds 40 years.
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PMID:Lowe syndrome. 1672 54