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R J Simensen

Publications and source records attributed to R J Simensen.

At least 19 recordsLinked to original sources
PubMed2006

Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia, and multiple congenital anomalies.

We have studied a male patient with significant developmental delay, growth failure, hypotonia, girdle weakness, microcephaly, and multiple congenital anomalies including atrial (ASD) and ventricular (VSD) septal defects. Detailed cytogenetic and molecular analyses revealed three de novo X chromosome aberrations and a karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32 approximately q22.2)del(X)(q22.3q22.3) was determined. The three X chromosome aberrations in the patient include: a pericentric inversion (inv 1) that disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively affecting no genes; and an interstitial deletion at Xq22.3 that results in functional nullisomy of several known genes, including a gene previously associated with X-linked nonsyndromic mental retardation, acyl-CoA synthetase long chain family member 4 (ACSL4). These findings suggest that the disruption of DMD and the absence of ACSL4 in the patient are responsible for neuromuscular disease and cognitive impairment.

Abnormalities, Multiple↗
PubMed2005

Renpenning syndrome comes into focus.

Renpenning syndrome represents a prototypic X-linked mental retardation condition with full expression of the phenotype in males and little or no expression in females. The predominant clinical findings are microcephaly, long narrow face, short stature with lean body build, and small testes. Mental retardation, usually of severe degree, occurs in 95% of cases. Less than 20% of cases have major malformations, the most common being cardiac defects and cleft palate. Subsequent to the description of mutations in the polyglutamine tract binding protein 1 (PQBP1) in Sutherland-Haan syndrome, Hamel cerebropalatocardiac syndrome, MRX55, and two small XLMR families, a single nucleotide insertion has been found in the original family with Renpenning syndrome and an AGAG deletion in a second family with the Renpenning syndrome. Mutations have also been found in Golabi-Ito-Hall syndrome, Porteous syndrome, and an additional small family. It is now demonstrated that five named XLMR syndromes (Sutherland-Haan, Hamel cerebropalatocardiac, Golabi-Ito-Hall, Porteous, and Renpenning), one nonsyndromic family (MRX55), and three small XLMR families have PQBP1 mutations and are thus allelic XLMR entities. In acknowledgement of the historical importance of the original report of Renpenning syndrome [1962], we propose that the entities with PQBP1 mutations be combined under the name of Renpenning syndrome.

Abnormalities, Multiple↗
PubMed2003

A prenatal counseling conundrum: mosaic trisomy 16. A case study presenting cognitive functioning and adaptive behavior.

We report developmental data on a patient prenatally diagnosed with mosaic trisomy 16. At age six years her intellectual functioning, academic achievement, and adaptive behavior are normal. The myriad of findings among cases prenatally diagnosed with mosaic trisomy 16 are discussed. The diagnosis presents a dilemma for genetic counselors and clinicians.

Child, Preschool↗
PubMed2002

Cognitive function in Coffin-Lowry syndrome.

Coffin-Lowry syndrome (CLS) is an X-linked disorder associated with mental retardation, distinctive facies and hands, hypotonia, and skeletal abnormalities. The syndrome results from mutations in the RSK2 gene located in Xp22.2. Although the syndrome has been elucidated clinically, few, if any, studies have focused on the cognitive deficits of the affected males or carrier females. The subjects of the present study were selected from two African-American families who have the same missense mutation (C340T) in RSK2. The subjects included six affected males, seven carrier females, three normal males and three non-carrier (normal) females. Normal family members served as contrast/comparison cohorts to control for socio-economic, sociocultural and genetic variables which would impinge on intellectual abilities. Analysis of cognitive function, as measured by the Stanford-Binet Intelligence Scale, 4th edn, demonstrated a distinct hierarchy of abilities from normal to carrier to affected patients. The mean composite IQs of the cohorts were 90.8, 65.0 and 43.2 for normal, carrier and affected individuals, respectively. These findings lend support to the clinical concept of negative intellectual effects in carriers of certain X-linked mental retardation conditions. X-inactivation studies showed that carrier females had mild to significant skewing. Normal females in the family did not demonstrate skewing. The correlation coefficient between IQ and X-inactivation status among carriers was not significant.

Black or African American↗
PubMed2000

The HOPA gene dodecamer duplication is not a significant etiological factor in autism.

A recent study has suggested that a dodecamer duplication in the HOPA gene in Xq13 may occur in a significant portion of male patients with autism. We have determined the incidence of this duplication in 202 patients from the South Carolina Autism Study. The incidence of the duplication was not significantly different between patients and controls. Three of the female patients inherited the duplication from nonautistic fathers. In addition, there was no systematic skewing of X inactivation in the female patients with the duplication, or in nonautistic mothers and sisters with the duplication. These findings suggest that the dodecamer duplication in the HOPA gene does not play a significant role in the etiology of autism.

Adult↗
PubMed1999

Gene for apparently nonsyndromic X-linked mental retardation (MRX32) maps to an 18-Mb region of Xp21.2-p22.

We studied a family with 11 males having X-linked mental retardation (XLMR) using microsatellite markers. Aside from the mental retardation, the affected males do not appear to differ from their unaffected brothers or uncles. The gene for this XLMR condition has been linked to DXS451 in Xp22.13 with a lod score of 5.18 at straight theta = 0. Recombination was detected at DXS992 (Xp21.3) and DXS1053 (Xp22.2), thereby defining the limits of the localization. This family is considered to have nonsyndromic XLMR and has been assigned the designation MRX32.

Adolescent↗
PubMed1998

Autism and maternally derived aberrations of chromosome 15q.

Of the chronic mental disabilities of childhood, autism is causally least well understood. The former view that autism was rooted in exposure to humorless and perfectionistic parenting has given way to the notion that genetic influences are dominant underlying factors. Still, identification of specific heritable factors has been slow with causes identified in only a few cases in unselected series. A broad search for genetic and environmental influences that cause or predispose to autism is the major thrust of the South Carolina Autism Project. Among the first 100 cases enrolled in the project, abnormalities of chromosome 15 have emerged as the single most common cause. The four abnormalities identified include deletions and duplications of proximal 15q. Other chromosome aberrations seen in single cases include a balanced 13;16 translocation, a pericentric inversion 12, a deletion of 20p, and a ring 7. Candidate genes involved in the 15q region affected by duplication and deletion include the ubiquitin-protein ligase (UBE3A) gene responsible for Angelman syndrome and genes for three GABA(A) receptor subunits. In all cases, the deletions or duplications occurred on the chromosome inherited from the mother.

Adolescent↗
PubMed1995

Deletion involving D15S113 in a mother and son without Angelman syndrome: refinement of the Angelman syndrome critical deletion region.

Deletions of 15q11-q13 typically result in Angelman syndrome when inherited from the mother and Prader-Willi syndrome when inherited from the father. The critical deletion region for Angelman syndrome has recently been restricted by a report of an Angelman syndrome patient with a deletion spanning less than 200 kb around the D15S113 locus. We report here on a mother and son with a deletion of chromosome 15 that includes the D15S113 locus. The son has mild to moderate mental retardation and minor anomalies, while the mother has a borderline intellectual deficit and slightly downslanting palpebral fissures. Neither patient has the seizures, excessive laughter and hand clapping, ataxia or the facial anomalies which are characteristic of Angelman syndrome. The proximal boundary of the deletion in our patients lies between the D15S10 and the D15S113 loci. Our patients do not have Angelman syndrome, despite the deletion of the D15S113 marker. This suggests that the Angelman syndrome critical deletion region is now defined as the overlap between the deletion found in the previously reported Angelman syndrome patient and the region that is intact in our patients.

Angelman Syndrome↗
PubMed1994

Aarskog-Scott syndrome: confirmation of linkage to the pericentromeric region of the X chromosome.

Aarskog-Scott syndrome was tentatively mapped to Xq13 on the basis of an X:8 translocation by Bawle et al. [Am J Med Genet 17:595-602, 1984]. A review of the cytogenetics and the use of molecular markers in that family have resulted in revision of the breakpoints of the translocation to Xp 11.2 and 8q11.21 [Glover et al., Hum Mol Genet 2:1717-1718, 1993]. Two families, including one of the two initial families with Aarskog-Scott syndrome [Scott, BD:OAS VII (6): 240-246, 1971], have participated in our study to evaluate the localization of the gene for Aarskog-Scott syndrome to the pericentromeric region of the X chromosome. Using a series of DNA probes, we have been able to confirm linkage to the X chromosome, with multipoint analysis indicating the most likely localization of the gene to be on the proximal short arm.

Abnormalities, Multiple↗
PubMed1994

Asymmetry of methylation with FMR-1 full mutation in two 45,X/46,XX mosaic females associated with normal intellect.

The full FMR-1 mutation is known to cause the fragile X syndrome [Fra(X)], but variable expression in females, including normal to deficient intellect, may be related to random X-inactivation (lyonization). We have evaluated 2 mosaic 45,X/46,XX females who are cytogenetically fra(X) positive, have an FMR-1 full mutation, and are of normal intellect. There were 50% fra(X) chromosomes in the 45,X cells of one of the females; this has not been reported previously. In both patients, there was a strong asymmetry of FMR-1 methylation with the normal allele being totally or 90% unmethylated and the mutant allele being similarly methylated. Thus, the apparent selective inactivation of the full mutant FMR-1 allele appears to have resulted in limited expression with normal intellect. The presence of the fra(X) chromosome in 45,X cells is unique; however, there may be no relationship to the asymmetric inactivation of the mutant allele which could be due to chance or a mechanism yet to be delineated.

Adolescent↗
PubMed1993

Fragile-X syndrome.

Explore the source record for details and available documents.

DNA Mutational Analysis↗
PubMed1990

Allan-Herndon syndrome. I. Clinical studies.

A large family with X-linked mental retardation, originally reported in 1944 by Allan, Herndon, and Dudley, has been reinvestigated. Twenty-nine males have been affected in seven generations. Clinical features include severe mental retardation, dysarthria, ataxia, athetoid movements, muscle hypoplasia, and spastic paraplegia with hyperreflexia, clonus, and Babinski reflexes. The facies appear elongated with normal head circumference, bitemporal narrowing, and large, simple ears. Contractures develop at both small and large joint. Statural growth is normal and macroorchidism does not occur. Longevity is not impaired. High-resolution chromosomes, serum creatine kinase, and amino acids are normal. This condition, termed the Allan-Herndon syndrome, appears distinct from other X-linked disorders having mental retardation, muscle hypoplasia, and spastic paraplegia.

Abnormalities, Multiple↗
PubMed1989

Fragile-X syndrome.

A fragile site on the X chromosome has been implicated in mental retardation and behavioral problems among both males and females. The fragile-X syndrome is second only to Down syndrome among causes of mental retardation associated with cytogenetic abnormalities. The clinical phenotype is extremely variable. During the early years, many affected children demonstrate normal or near-normal intellect and development. Folic acid may be of benefit before puberty.

Adult↗
PubMed1987

Fragile X syndrome: a common etiology of mental retardation.

Fragile X syndrome, second only to Down syndrome among etiologies of mental retardation, was discussed. Clinical, intellectual, and anthropometric characteristics from 67 fragile X positive males, 35 fragile X positive females, and 27 obligate carriers among 29 families was presented. Regression analysis showed little correlation between level of intellect and frequency of fragile sites. The mean IQ among the various age groups of male patients decreased with increasing age, and some intellectual deterioration could not be ruled out. Folic acid was suggested as a viable treatment mode among prepubescent males.

Female↗