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D Ross McLeod

Publications and source records attributed to D Ross McLeod.

7 recordsLinked to original sources
PubMed2005

Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification.

An autosomal recessive syndrome of nonprogressive cerebellar ataxia and mental retardation is associated with inferior cerebellar hypoplasia and mild cerebral gyral simplification in the Hutterite population. An identity-by-descent mapping approach using eight patients from three interrelated Hutterite families localized the gene for this syndrome to chromosome region 9p24. Haplotype analysis identified familial and ancestral recombination events and refined the minimal region to a 2-Mb interval between markers D9S129 and D9S1871. A 199-kb homozygous deletion encompassing the entire very low density lipoprotein receptor (VLDLR) gene was present in all affected individuals. VLDLR is part of the reelin signaling pathway, which guides neuroblast migration in the cerebral cortex and cerebellum. To our knowledge, this syndrome represents the first human lipoprotein receptor malformation syndrome and the second human disease associated with a reelin pathway defect.

Base Sequence↗
PubMed2005

High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome.

Germline mutations in the STK11 gene have been identified in 10-70% of patients with Peutz-Jeghers syndrome (PJS), an autosomal-dominant hamartomatous polyposis syndrome. A second locus was assumed in a large proportion of PJS patients. To date, STK11 alterations comprise mainly point mutations; only a small number of large deletions have been reported. We performed a mutation analysis for the STK11 gene in 71 patients. Of these, 56 met the clinical criteria for PJS and 12 were presumed to have PJS because of mucocutaneous pigmentation only or bowel problems due to isolated PJS polyps. No clinical information was available for the remaining three patients. By direct sequencing of the coding region of the STK11 gene, we identified point mutations in 37 of 71 patients (52%). We examined the remaining 34 patients by means of the multiplex ligation-dependent probe amplification (MLPA) method, and detected deletions in 17 patients. In four patients the deletion extended over all 10 exons, and in eight patients only the promoter region and exon 1 were deleted. The remaining deletions encompassed exons 2-10 (in two patients), exons 2-3, exons 4-5, or exon 8. When only patients who met the clinical criteria for PJS are considered, the overall mutation detection rate increases to 94% (64% point mutations and 30% large deletions). No mutation was identified in any of the 12 presumed cases. In conclusion, we found that approximately one-third of the patients who met the clinical PJS criteria exhibited large genomic deletions that were readily detectable by MLPA. Screening for point mutations and large deletions by direct sequencing or MLPA, respectively, increased the mutation detection rate in the STK11 gene up to 94%. There may be still other mutations in the STK11 gene that are not detectable by the methods applied here. Therefore, it is questionable whether a second PJS locus exists at all.

AMP-Activated Protein Kinase Kinases↗
PubMed2005

Autosomal recessive cerebellar hypoplasia in the Hutterite population.

Cerebellar hypoplasia is a rare malformation caused by a variety of etiologies. It usually manifests clinically as non-progressive cerebellar ataxia with or without mental retardation. We further characterize a syndrome of autosomal recessive cerebellar hypoplasia in the Hutterite population, referred to as dysequilibrium syndrome (DES). We reviewed 12 patients (eight females, four males; age range 4 to 33 y) with this syndrome. Patients were examined and underwent a standard set of investigations to characterize better the clinical features, natural history, and neuroimaging of this syndrome. DES is an autosomal recessive disorder with distinct clinical features including global developmental delay, late ambulation (after age 6 y), truncal ataxia, and a static clinical course. Neuroimaging is characterized by hypoplasia of the inferior portion of the cerebellar hemispheres and vermis, and mild simplification of cortical gyri.

Adolescent↗
PubMed2004

Autosomal dominant flat umbilicus.

We describe a Chinese family among whom five members in three generations had a flat umbilicus with vertical and male to male transmission indicative of autosomal dominant inheritance. Except the proband, who also had Tetralogy of Fallot, other affected members had a flat umbilicus as an isolated anomaly. Autosomal dominant transmission of isolated flat umbilicus has not been reported previously.

Adolescent↗
PubMed2002

Acute hemorrhagic leukoencephalitis in male sibs.

Male siblings developed acute hemorrhagic leukoencephalitis (AHL) at age five months and eight months, respectively. This rare condition has not been reported in individuals less than two years of age or with a recurrence in the family. The diagnosis was based on neuropathologic features after ruling out potentially mimicking conditions. Genetic counseling of early onset AHL should include the possibility of recurrence in siblings.

Female↗
PubMed2002

Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease.

Adolescent↗