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Erik T. Te Beek - One of the best experts on this subject based on the ideXlab platform.

  • tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
    Nature Genetics, 2008
    Co-Authors: Birgit Budde, Yasmin Namavar, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Bwee-tien Poll-the, Peter G. Barth, Christian Becker, Gudrun Nurnberg, Erik T. Te Beek
    Abstract:

    Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative Autosomal Recessive Disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological Disorders. Frank Baas and colleagues report mutations in three of the four subunits of the tRNA-splicing endonuclease complex in families with two subtypes of pontocerebellar hypoplasia. The findings implicate tRNA processing in neurological Disorders.

  • tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
    Nature Genetics, 2008
    Co-Authors: Birgit Budde, Yasmin Namavar, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Bwee-tien Poll-the, Peter G. Barth, Christian Becker, Gudrun Nurnberg, Erik T. Te Beek
    Abstract:

    Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative Autosomal Recessive Disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological Disorders.

M. De Braekeleer - One of the best experts on this subject based on the ideXlab platform.

  • Autosomal Recessive Disorders in Saguenay-Lac-Saint-Jean (Quebec, Canada): a study of inbreeding.
    Annals of human genetics, 1996
    Co-Authors: M. De Braekeleer, S. Gauthier
    Abstract:

    Summary Saguenay Lac-Saint-Jean (SLSJ) is a geographically isolated region of northeastern Quebec in which several Autosomal Recessive Disorders have a high incidence. We calculated the inbreeding coefficients of 567 probands and compared them to 1701 matched control individuals. The mean inbreeding coefficient of the group containing all 567 probands was 2·73 times higher than that of the controls (0·001772 versus 0·00065). Thirteen percent (75/567) of the probands were inbred, but only 5% were born to matings between spouses related as second-degree cousins or closer. No marriage between uncle and niece and only two marriages between first-degree cousins were identified in the disorder group. These results strongly suggest that the high incidence of the Autosomal Recessive Disorders in SLSJ is the result of a founder effect.

  • Autosomal Recessive Disorders in Saguenay-Lac-St-Jean, Quebec: study of kinship.
    Human biology, 1996
    Co-Authors: M. De Braekeleer, S. Gauthier
    Abstract:

    Saguenay-Lac-St-Jean is a geographically isolated region of northeastern Quebec in which several Autosomal Recessive Disorders have a high incidence. The kinship coefficients of all possible pairs of 567 probands were calculated and compared with those of 1701 matched control individuals. The mean kinship coefficient of the group containing all 567 probands was 5.57 times higher than that of the control group (0.000981 versus 0.000176). Overall, 45.5% of the probands were third-degree cousins, compared with 32.9% of the control group. However, in each disorder only a few probands were traced back to the most represented founder couple in Saguenay-Lac-St-Jean. Molecular data added a new dimension to the concept of kinship by showing that at least in the study area, closely related individuals do not necessarily carry identical mutations, which, in turn, may have a great impact on carrier screening. Our results strongly suggest that the high incidence of Autosomal Recessive Disorders in Saguenay-Lac-St-Jean is the result of a founder effect.

  • Autosomal Recessive Disorders in Saguenay-Lac-Saint-Jean (Quebec, Canada): estimation of inbreeding from isonymy.
    Annals of human biology, 1996
    Co-Authors: M. De Braekeleer
    Abstract:

    SummaryThe total inbreeding coefficient of a group of 574 individuals with Autosomal Recessive Disorders (ARD) from Saguenay-Lac-Saint-Jean, a geographically isolated region of northeastern Quebec, was estimated from isonymy and compared to the mean inbreeding coefficient calculated from the genealogies. Its value was compared to that of 1722 matched controls. The total inbreeding coefficient was similar in both ARD and control groups, but higher than the values calculated from the genealogies. Most of the increase was due to the random component of inbreeding. This isonymy study confirmed that the high frequency of ARD in Saguenay-Lac-Saint-Jean is mainly the result of founder effect and genetic drift.

  • Geographic distribution of 18 Autosomal Recessive Disorders in the French Canadian population of Saguenay-Lac-Saint-Jean, Quebec.
    Annals of human biology, 1995
    Co-Authors: M. De Braekeleer
    Abstract:

    SummaryWe analysed the geographic distribution of 770 patients and 1084 obligate carriers of 18 Autosomal Recessive Disorders that have a high incidence in Saguenay-Lac-Saint-Jean (SLSJ) (Quebec). The places of birth of the patients and the obligate carriers were found to be unevenly distributed in SLSJ. A statistically significant higher number of places of birth than expected (p ≤ 0·05) was observed in Saguenay and Lac-Saint-Jean (LSJ) East, where the immigration was mainly the fact of individuals coming from Charlevoix. A significantly lower number of places of birth than expected was found in LSJ West, and in some municipalities in which the immigration and the contribution of the ancestors from Charlevoix was low. The geographic distribution of inbreeding and kinship only partially explained the geographic distribution of the Disorders. The individuals who had both parents and all four grandparents born in SLSJ were at a higher risk of having a Recessive disorder. While the genes of these Disorders a...

S. Gauthier - One of the best experts on this subject based on the ideXlab platform.

  • Autosomal Recessive Disorders in Saguenay-Lac-Saint-Jean (Quebec, Canada): a study of inbreeding.
    Annals of human genetics, 1996
    Co-Authors: M. De Braekeleer, S. Gauthier
    Abstract:

    Summary Saguenay Lac-Saint-Jean (SLSJ) is a geographically isolated region of northeastern Quebec in which several Autosomal Recessive Disorders have a high incidence. We calculated the inbreeding coefficients of 567 probands and compared them to 1701 matched control individuals. The mean inbreeding coefficient of the group containing all 567 probands was 2·73 times higher than that of the controls (0·001772 versus 0·00065). Thirteen percent (75/567) of the probands were inbred, but only 5% were born to matings between spouses related as second-degree cousins or closer. No marriage between uncle and niece and only two marriages between first-degree cousins were identified in the disorder group. These results strongly suggest that the high incidence of the Autosomal Recessive Disorders in SLSJ is the result of a founder effect.

  • Autosomal Recessive Disorders in Saguenay-Lac-St-Jean, Quebec: study of kinship.
    Human biology, 1996
    Co-Authors: M. De Braekeleer, S. Gauthier
    Abstract:

    Saguenay-Lac-St-Jean is a geographically isolated region of northeastern Quebec in which several Autosomal Recessive Disorders have a high incidence. The kinship coefficients of all possible pairs of 567 probands were calculated and compared with those of 1701 matched control individuals. The mean kinship coefficient of the group containing all 567 probands was 5.57 times higher than that of the control group (0.000981 versus 0.000176). Overall, 45.5% of the probands were third-degree cousins, compared with 32.9% of the control group. However, in each disorder only a few probands were traced back to the most represented founder couple in Saguenay-Lac-St-Jean. Molecular data added a new dimension to the concept of kinship by showing that at least in the study area, closely related individuals do not necessarily carry identical mutations, which, in turn, may have a great impact on carrier screening. Our results strongly suggest that the high incidence of Autosomal Recessive Disorders in Saguenay-Lac-St-Jean is the result of a founder effect.

Joel Zlotogora - One of the best experts on this subject based on the ideXlab platform.

  • Forty seven pathogenic variants causing Autosomal Recessive Disorders are shared by Israeli and Saudi Arabian Arabs
    Clinical genetics, 2021
    Co-Authors: Joel Zlotogora
    Abstract:

    Several Autosomal Recessive Disorders that are found among Arabs in Israel were also reported in Saudi Arabia. In a sytematic review of all the variants responsible for Autosomal Recessive Disorders among Muslim Arabs Israel and in Saudi Arabia, 47 shared variants were found, many being known founder variants in both populations. Among the 21 shared variants that were reported among Bedouins 14 were founder variants representing 14% founder/assumed founder variants known in the Bedouins. Many of the common variants are ancient having a Bedouin origin probably linked to the migration from the Saudi Peninsula. It is probable that a similar phenomenon occurred along the route of the Bedouin migrations and indeed some of these variants are present in the corresponding populations.

  • ashkenazi jewish genomic variants integrating data from the israeli national genetic database and gnomad
    Genetics in Medicine, 2018
    Co-Authors: Joel Zlotogora, George P Patrinos, Vardiella Meiner
    Abstract:

    The aim of the study was to compare the data for mutations related to clinical Disorders reported among Ashkenazi Jewish patients in the Israeli National Genetic Database (INGD) with variants included in the Genome Aggregation Database (gnomAD). We extracted data for mutations claimed to cause Disorders reported among Ashkenazi Jews from the INGD and searched gnomAD for each of them. We compared the allele frequency of each variant in Ashkenazi Jews with that of other delineated populations. Of the 58 INGD-reported mutations related to Autosomal-dominant Disorders, 19 were present in gnomAD (32.8%). Of the 309 mutations related to Autosomal-Recessive Disorders, 240 (77.7%) were variants found in gnomAD. Of these variants, 202 (84.2%) were documented among one or more Ashkenazi individuals. At this point in the INGD, there are 168 Ashkenazi assumed founder mutations in 128 different genes corresponding to 111 Autosomal-Recessive Disorders. Integration of information on mutations among Ashkenazi Jews extracted from the INGD with their population frequency recorded in gnomAD is important for effective straightforward molecular diagnosis as well as for targeted carrier screening either for reproductive decision-making or for implementation of disease-modifying behavior.

  • genetic Disorders among palestinian arabs 1 effects of consanguinity
    American Journal of Medical Genetics, 1997
    Co-Authors: Joel Zlotogora
    Abstract:

    Among Palestinian Arabs the rate of consanguinity is very high and some 44.3% of the marriages are between relatives (22.6% of them between first cousins). In almost 2,000 files from Palestinian Arab families who attended the genetics clinic in the Hadassah Medical Center; we were able to study the effects of consanguinity on different Disorders. The consanguinity rate in families with dominant or X-linked Disorders and chromosome aberrations was similar to the one observed in the general population. We did not find any significant differences in the rate of consanguineous marriages between the parents and grandparents of children affected with trisomy 21 and the general population. Thus, we were not able to confirm the suggestion that there is an increase risk for trisomies in children/grandchildren of consanguineous parents. Among the parents of patients with rare Autosomal Recessive Disorders the consanguinity rate was much higher than the one of the general population (92.5%). Among the Autosomal Recessive Disorders, which were relatively frequent in the population, there were fewer marriages between relatives; but in most cases the difference from rare Disorders is relatively small. The importance of genetic factors in various congenital malformations, such as neural tube defects and cleft lip/palate or in various forms of infertility, was confirmed by the observation of a significantly higher consanguinity rate in the parents of these patients than is observed in the general population.

Birgit Budde - One of the best experts on this subject based on the ideXlab platform.

  • tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
    Nature Genetics, 2008
    Co-Authors: Birgit Budde, Yasmin Namavar, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Bwee-tien Poll-the, Peter G. Barth, Christian Becker, Gudrun Nurnberg, Erik T. Te Beek
    Abstract:

    Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative Autosomal Recessive Disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological Disorders. Frank Baas and colleagues report mutations in three of the four subunits of the tRNA-splicing endonuclease complex in families with two subtypes of pontocerebellar hypoplasia. The findings implicate tRNA processing in neurological Disorders.

  • tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
    Nature Genetics, 2008
    Co-Authors: Birgit Budde, Yasmin Namavar, Fred Van Ruissen, Marian A. J. Weterman, Kees Fluiter, Bwee-tien Poll-the, Peter G. Barth, Christian Becker, Gudrun Nurnberg, Erik T. Te Beek
    Abstract:

    Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative Autosomal Recessive Disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological Disorders.