Spherophakia associated with molybdenum cofactor deficiency

Parini, Rossella; Briscioli, Vincenza; Caruso, U.; Dorche, C.; Fortuna, Renato; Minniti, G.; Selicorni, Angelo; Vismara, Elisabetta; Mancini, Grazia M.S.

doi:10.1002/(sici)1096-8628(19971219)73:3<272::aid-ajmg8>3.0.co;2-u

Cited by 14 publications

(9 citation statements)

References 9 publications

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“…We could not identify a MOCS1 mutation in the individuals reported by Bonioli et al (1996) and Gray et al (1990). One patient homozygous for the MOCS1 B mutation 1523delAG has been described recently by Parini et al (1997). A definitive diagnosis was only made when the patient was 8 years of age, because of the development of lens dislocation, which is a prominent but not obligate consequence of MoCo deficiency.…”

Section: Discussionmentioning

confidence: 97%

Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A

et al. 1998

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Molybdenum cofactor (MoCo) deficiency is a rare and devastating disease resulting in neonatal seizures and other neurological symptoms identical to those of sulphite oxidase deficiency. It is an autosomal recessive disease and no therapy is known. Most patients harbour MOCS1 mutations, which are found in both open reading frames of this unusual gene encoding the first two enzymes required in the MoCo biosynthesis pathway, MOCS1 A and MOCS1 B, in a single transcript. We describe genomic details as a prerequisite for comprehensive mutation analysis. In an initial cohort of 24 MoCo deficiency patients, we identified 13 different mutations on 34 chromosomes, with a mutation detection rate of 70%. Five mutations were observed in more than one patient and together accounted for two thirds of detected mutations. These comprise the most frequent mutation, R319Q, which is restricted to England, two Danish/German mutations (one missense and one splice site mutation), a missense mutation found in England and Germany, and a "Mediterranean" frameshift mutation. All patients with identified mutations are either homozygous or compound heterozygous for mutations in either of the two open reading frames corresponding to MOCS1 A and MOCS1 B, respectively. This observation suggests the existence of more than the two previously described complementation groups in MoCo biosynthesis.

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Section: Discussionmentioning

confidence: 97%

Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A

et al. 1998

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“…26,27 The fact that patients with MoCD develop lens dislocation late at the age of approximately 8 years may be the reason for the lack of this finding in our cohort as all our patients are well below this average age. 28 …”

Section: Discussionmentioning

confidence: 99%

Molybdenum cofactor and isolated sulphite oxidase deficiencies: Clinical and molecular spectrum among Egyptian patients

Zaki

Selim

El-Bassyouni

et al. 2016

European Journal of Paediatric Neurology

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Aim Molybdenum cofactor deficiency (MoCD) and Sulfite oxidase deficiency (SOD) are rare autosomal recessive conditions of sulfur-containing amino acid metabolism with overlapping clinical features and emerging therapies. The clinical phenotype is indistinguishable and they can only be differentiated biochemically. MOCS1, MOCS2, MOCS3, and GPRN genes contribute to the synthesis of molybdenum cofactor, and SUOX gene encodes sulfite oxidase. The aim of this study was to elucidate the clinical, radiological, biochemical and molecular findings in patients with SOD and MoCD. Methods Detailed clinical and radiological assessment of 9 cases referred for neonatal encephalopathy with hypotonia, microcephaly, and epilepsy led to a consideration of disorders of sulfur-containing amino acid metabolism. The diagnosis of six with MoCD and three with SOD was confirmed by biochemical tests, targeted sequencing, and whole exome sequencing where suspicion of disease was lower. Results Novel SUOX mutations were detected in 3 SOD cases and a novel MOCS2 mutation in 1 MoCD case. Most patients presented in the first 3 months of life with intractable tonic–clonic seizures, axial hypotonia, limb hypertonia, exaggerated startle response, feeding difficulties, and progressive cystic encephalomalacia on brain imaging. A single patient with MoCD had hypertrophic cardiomyopathy, hitherto unreported with these diseases. Interpretation Our results emphasize that intractable neonatal seizures, spasticity, and feeding difficulties can be important early signs for these disorders. Progressive microcephaly, intellectual disability and specific brain imaging findings in the first year were additional diagnostic aids. These clinical cues can be used to minimize delays in diagnosis, especially since promising treatments are emerging for MoCD type A.

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“…The first 15 patients have been summarized elsewhere [Johnson and Wadman, 1989]. Further reports followed [Appignani et al, 1996; Arnold et al, 1993; Coskun et al, 1998; Hahnewald et al, 2006; Ichida et al, 2001, 2006; Kavukcu et al, 2000; Leimkuhler et al, 2005; Macaya et al, 2005; Parini et al, 1997; Per et al, 2007; Pintos‐Morell et al, 1995; Salman et al, 2002; Salvan et al, 1999; Sass et al, 2010; Schuierer et al, 1995; Serrano et al, 2007; Slot et al, 1993; Teksam et al, 2005; van Gennip et al, 1994].…”

Section: Phenotype and Diagnosismentioning

confidence: 99%

Molybdenum cofactor deficiency: Mutations in GPHN, MOCS1, and MOCS2

2010

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All molybdenum‐containing enzymes other than the bacterial nitrogenase share an identical molybdenum cofactor (MoCo), which is synthesized via a conserved pathway in all organisms and therefore also is called “universal molybdenum cofactor.” In humans, four molybdoenzymes are known: aldehyde oxidase, mitochondrial amidoxime reducing component (mARC), xanthine oxidoreductase, and sulfite oxidase. Mutations in the genes encoding the biosynthetic MoCo pathway enzymes abrogate the activities of all molybdoenzymes and result in the “combined” form of MoCo deficiency, which is clinically very similar to isolated sulfite oxidase deficiency, caused by mutations in the gene for the corresponding apoenzyme. Both deficiencies are inherited as an autosomal‐recessive disease and result in progressive neurological damage and early childhood death in most cases. The majority of mutations leading to MoCo deficiency have been identified in the genes MOCS1 (type A deficiency), MOCS2 (type B deficiency), with one reported in GPHN. For type A deficiency an effective substitution therapy has been described recently. Hum Mutat 32:10–18, 2011. © 2010 Wiley‐Liss, Inc.

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Spherophakia associated with molybdenum cofactor deficiency

Cited by 14 publications

References 9 publications

Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A

Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A

Molybdenum cofactor and isolated sulphite oxidase deficiencies: Clinical and molecular spectrum among Egyptian patients

Molybdenum cofactor deficiency: Mutations in GPHN, MOCS1, and MOCS2

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