RESUMEN

Celiac disease is a common, familial autoimmune disease caused by exposure to gliadin in wheat, and related prolamins in barley and rye. The prevalence of the disease is approximately 1:133. Celiac disease can cause significant morbidity. The only treatment is a gluten-free diet. A genome-wide search of 405 microsatellite markers was performed on samples from 18 Bedouin families with a minimum of two cases of celiac disease. Non-parametric and parametric (including both dominant and recessive models of inheritance) linkage analyses were performed. The most significant genome-wide linkage evidence was at chromosome 3p26 with an HLod of 3.21, under the dominant model. The only other HLod or NPL greater than 2 was at 4q35, with an HLod of 2.15 under a dominant model. The region at 3p26, previously reported in two linkage analyses, harbors interleukin receptor genes, plausible candidates for celiac disease.

Asunto(s)

Árabes/genética , Enfermedad Celíaca/genética , Familia , Pruebas Genéticas , Genoma Humano , Cromosomas Humanos Par 3 , Cromosomas Humanos Par 4 , Genes Dominantes , Genes Recesivos , Heterogeneidad Genética , Ligamiento Genético , Marcadores Genéticos , Haplotipos , Humanos , Escala de Lod , Repeticiones de Microsatélite , Modelos Genéticos , Linaje , Estadísticas no Paramétricas

RESUMEN

We report unusual congenital ichthyosiform dermatosis in 5 of 12 children in two related families of unaffected, consanguineous Bedouin parents. It appeared shortly after birth as a fine peeling of nonerythematous skin on palms and soles. Gradually it evolved into prominent, well-demarcated areas of peeling skin in moist and traumatized regions. The cutaneous manifestations share features of ichthyosis bullosa of Siemens (IBS) and peeling skin syndrome (PSS). Histologic examination revealed orthokeratosis, a thickened granular cell layer, and spongiosis without epidermolytic hyperkeratosis. On electron microscopy there was prominent intercellular edema and numerous aggregates of keratin filaments in basal keratinocytes. This combination of clinical, histologic, and ultrastructural features has not been previously reported in the heterogeneous group of congenital ichthyoses. We suggest that it represents a new variant of exfoliative ichthyosis.

Asunto(s)

Genes Recesivos , Ictiosis/genética , Adolescente , Fármacos Dermatológicos/uso terapéutico , Femenino , Humanos , Ictiosis/diagnóstico , Ictiosis/tratamiento farmacológico , Ictiosis/patología , Lactante , Recién Nacido , Masculino , Linaje

RESUMEN

Bardet-Biedl syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease. Six distinct BBS loci map to 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although BBS is rare in the general population (<1/100,000), there is considerable interest in identifying the genes causing BBS because components of the phenotype, such as obesity and diabetes, are common. We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects). MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum. We recently identified a novel gene that causes BBS2. The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4.

Asunto(s)

Síndrome de Bardet-Biedl/genética , Obesidad/genética , Proteínas/genética , Clonación Molecular , Consanguinidad , Etiquetas de Secuencia Expresada , Humanos , Proteínas Asociadas a Microtúbulos , Datos de Secuencia Molecular , Mutación

RESUMEN

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder with the primary clinical features of obesity, pigmented retinopathy, polydactyly, hypogenitalism, mental retardation and renal anomalies. Associated features of the disorder include diabetes mellitus, hypertension and congenital heart disease. There are six known BBS loci, mapping to chromosomes 2, 3, 11, 15, 16 and 20. The BBS2 locus was initially mapped to an 18 cM interval on chromosome 16q21 with a large inbred Bedouin kindred. Further analysis of the Bedouin population allowed for the fine mapping of this locus to a 2 cM region distal to marker D16S408. Physical mapping and sequence analysis of this region resulted in the identification of a number of known genes and expressed sequence tag clusters. Mutation screening of a novel gene (BBS2) with a wide pattern of tissue expression revealed homozygous mutations in two inbred pedigrees, including the large Bedouin kindred used to initially identify the BBS2 locus. In addition, mutations were found in three of 18 unrelated BBS probands from small nuclear families.

Asunto(s)

Síndrome de Bardet-Biedl/genética , Cromosomas Humanos Par 16 , Secuencia Conservada , Secuencia de Aminoácidos , Animales , Mapeo Cromosómico , Clonación Molecular , Evolución Molecular , Femenino , Pruebas Genéticas , Humanos , Masculino , Ratones , Datos de Secuencia Molecular , Mutación , Linaje , Proteínas/genética , Ratas

RESUMEN

The combined DFNB7-DFNB11 deafness locus maps to chromosome 9q13-q21 between markers D9S1806 and D9S769. We have determined the cDNA sequence and genomic structure of a novel gene, TMEM2, that maps to this interval and is expressed in the cochlea. The mouse orthologue of this gene (Tmem2) maps to the murine dn (deafness) locus on mouse chromosome 19. Screens for transmembrane helices reveal the presence of at least one putative transmembrane domain in the TMEM2 protein. To determine whether mutations in TMEM2 cause hearing loss at the DFNB7-DFNB11 locus, we screened the coding region of this gene in DFNB7-DFNB11 affected families by direct sequencing. All DNA variants that segregated with the deafness and changed the predicted amino acid sequence of TMEM2 were common polymorphisms, as demonstrated by allele-specific amplification of pooled control DNA. Northern blot analysis showed no difference in transcript size or expression level of Tmem2 in dn/dn and control mice. The intragenic polymorphisms in TMEM2 represent a novel centromeric boundary for the DFNB7-DFNB11 interval.

Asunto(s)

Cromosomas Humanos Par 9/genética , Sordera/genética , Genes/genética , Proteínas de la Membrana/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Northern Blotting , Mapeo Cromosómico , Cromosomas/genética , Cóclea/embriología , Cóclea/metabolismo , Mapeo Contig , ADN/química , ADN/genética , Análisis Mutacional de ADN , ADN Complementario/química , ADN Complementario/genética , Exones , Salud de la Familia , Femenino , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Humanos , Intrones , Masculino , Ratones , Datos de Secuencia Molecular , Mutación , Linaje , Polimorfismo Genético , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Secuencia de ADN , Distribución Tisular

RESUMEN

Isolated growth hormone deficiency (IGHD) IB is an autosomal recessive disorder characterized by a good response to exogenous growth hormone (GH) treatment without development of anti-GH antibodies. Patients with IGHD IB were found to be compound heterozygotes for deletion and frameshift mutations as well as homozygotes for splicing mutations in the GH-1 gene. Recently, a novel splicing mutation in the GH-1 gene was identified in an extended, consanguineous Arab-Bedouin family from Israel with IGHD IB. Prior to the identification of this mutation, a considerable number of children with short stature in this family were found normal on pharmacological stimulation for GH release. This observation prompted a genotype/phenotype correlation of potential heterozygotes in the family. Carriers of the mutant GH-1 allele were found as a group to have a significantly shorter stature than normal homozygote (mean standard deviation scores, 1.67 and -0.40, respectively, P<0.05). Moreover, 11 of 33 (33%) heterozygotes, but only 1 of 17 (5.9%) normal homozygotes, had their height at 2 or more SD below the mean. Overall, 48.5% of studied heterozygotes were found to be of appreciably short stature with height at or lower than the 5th centile (> or = -1.7 SD), whereas only 5.9% of the normal homozygotes did (P<0.004). This phenomenon of heterozygotes for a recessive mutation in the GH-1 gene manifesting short stature, might imply that some such mutations may account for non-GH deficiency reduced height in the general population.

Asunto(s)

Estatura/genética , Mutación del Sistema de Lectura , Genes Recesivos , Tamización de Portadores Genéticos , Hormona del Crecimiento/deficiencia , Femenino , Homocigoto , Humanos , Masculino , Linaje , Fenotipo

RESUMEN

The DFNB7/11 locus for autosomal recessive non-syndromic hearing loss (ARNSHL) has been mapped to an approx. 1.5 Mb interval on human chromosome 9q13-q21. We have determined the cDNA sequence and genomic structure of a novel cochlear-expressed gene, ZNF216, that maps to the DFNB7/11 interval. The mouse orthologue of this gene maps to the murine dn (deafness) locus on mouse chromosome 19. The ZNF216 gene is highly conserved between human and mouse, and contains two regions that show homology to the putative zinc linger domains of other proteins. To determine it mutations in ZNF216 might be the cause of hearing loss at the DFNB7/11 locus, we screened the coding region of this gene in DFNB7/11 families by direct sequencing. No potential disease-causing mutations were found. In addition, Northern blot analysis showed no difference in ZNF216 transcript size or abundance between dn and control mice. These data Suggest that the ZNF216 gene is unlikely to be responsible for hearing loss at the DFNB7/11 and dn loci.

Asunto(s)

Mapeo Cromosómico , Cromosomas Humanos Par 19 , Cóclea/metabolismo , Pérdida Auditiva/genética , Proteínas/genética , Algoritmos , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Cromosomas Artificiales de Levadura , Análisis Mutacional de ADN , Proteínas de Unión al ADN , Exones , Feto , Genes Recesivos , Proyecto Genoma Humano , Humanos , Intrones , Ratones , Datos de Secuencia Molecular , Biosíntesis de Proteínas , Proteínas/química , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Dedos de Zinc

RESUMEN

Autosomal recessive osteopetrosis is a rare congenital disorder characterized by the development of abnormally dense bones, acrocephaly, severe anemia, hepatosplenomegaly and progressive deafness and blindness. The clinical course is rapidly progressive and is lethal at a very young age in the absence of a bone marrow transplant. The failure to remodel developing bone that is the basis of the disease process is most likely due to a dysfunction of the bone resorptive cell, the osteoclast. This phenotype is similar to that of the murine mutation osteosclerosis (oc), which is localized to proximal mouse chromosome 19. Given the similarity between the human and murine phenotypes, we tested whether human osteopetrosis maps to a region of conserved synteny. Microsatellite markers in the region of 11q12-13 were found to be linked to osteopetrosis in two consanguineous Bedouin kindreds. Recombination events were used to define the disease interval to an approximately 14 cM region between D11S1983 and D11S2371. A maximum LOD score of 7. 94 was obtained with D11S449 at straight theta = 0.

Asunto(s)

Cromosomas Humanos Par 11/genética , Osteopetrosis/genética , Osteosclerosis/genética , Animales , Niño , Preescolar , Mapeo Cromosómico , Consanguinidad , Modelos Animales de Enfermedad , Femenino , Genes Recesivos , Humanos , Lactante , Escala de Lod , Masculino , Ratones , Repeticiones de Microsatélite , Mutación , Osteopetrosis/congénito , Linaje

RESUMEN

Mutations in the Cx26 gene have been shown to cause autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNB1 locus on chromosome 13q12. Using direct sequencing, we screened the Cx26 coding region of affected and nonaffected members from seven ARNSHL families either linked to the DFNB1 locus or in which the ARNSHL phenotype cosegregated with markers from chromosome 13q12. Cx26 mutations were found in six of the seven families and included two previously described mutations (W24X and W77X) and two novel Cx26 mutations: a single base pair deletion of nucleotide 35 resulting in a frameshift and a C-to-T substitution at nucleotide 370 resulting in a premature stop codon (Q124X). We have developed and optimized allele-specific PCR primers for each of the four mutations to rapidly determine carrier and noncarrier status within families. We also have developed a single stranded conformational polymorphism (SSCP) assay which covers the entire Cx26 coding region. This assay can be used to screen individuals with nonsyndromic hearing loss for mutations in the CX26 gene.

Asunto(s)

Conexinas/genética , Genes Recesivos , Pérdida Auditiva Sensorineural/genética , Mutación , Alelos , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 13 , Conexina 26 , Femenino , Pérdida Auditiva Sensorineural/etnología , Humanos , Masculino , Medio Oeste de Estados Unidos/epidemiología , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Eliminación de Secuencia

RESUMEN

The remarkable progress in modern genetic technology enables the identification of genes causing devastating diseases and thereby the development of tools for prenatal diagnosis and carrier detection. To implement the results of genetic research in traditional societies, where genetic diseases are more prevalent due to inbreeding, necessitates a culturally appropriate approach that also promotes traditional and societal values important to the relevant community. This paper presents our experience with implementing the results of modern genetic research among the traditional community of the Negev Bedouin of Israel. Although the benefit of using those results for the prevention of genetic diseases seems obvious, successful implementation relies on a carefully designed educational program aimed at changing culturally related attitudes and perceptions. Such a program should attend to the needs of the community and be sensitive to its traditional values.

Asunto(s)

Árabes/genética , Consanguinidad , Enfermedades Genéticas Congénitas/etnología , Enfermedades Genéticas Congénitas/prevención & control , Investigación Genética/ética , Cultura , Tamización de Portadores Genéticos , Asesoramiento Genético , Pruebas Genéticas , Humanos , Israel

RESUMEN

DFNB7 and DFNB11, two loci for autosomal recessive nonsyndromic hearing loss (ARNSHL), have been mapped to chromosome 9q13-21 in separate consanguineous families. Using a radiation hybrid map, we have determined the correct marker order in the DFNB7/11 region and have demonstrated that the DFNB11 locus resides within a redefined DFNB7 interval. The gene(s) responsible for ARNSHL at these loci resides within an approximately 1 cM interval bounded by markers D9S1806 (centromeric) and D9S769 (telomeric). A recently discovered Indian family confirms the new telomeric boundary. To assist in the identification and cloning of candidate genes, YAC and PAC contigs were constructed. A total of 19 YAC and 23 PAC clones were utilized to span the affected region and ensure double coverage throughout. Twenty-two previously published STSs and 21 new STSs were used to determine marker order and confirm the integrity of the contig. Using a positional cloning strategy we have identified three cochlear expressed genes that map to the DFNB7/11 interval.

Asunto(s)

Mapeo Cromosómico , Cromosomas Humanos Par 9/ultraestructura , Expresión Génica , Pérdida Auditiva Bilateral/genética , Cromosomas Artificiales de Levadura , Consanguinidad , Femenino , Marcadores Genéticos , Genotipo , Pérdida Auditiva Bilateral/congénito , Homocigoto , Humanos , Masculino , Linaje , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Lugares Marcados de Secuencia

RESUMEN

Familial hypomagnesemia with secondary hypocalcemia (HSH) (MIM 307600) was studied in three inbred Bedouin kindreds from Israel. The three kindreds, one extended and two nuclear families, contained 13 affected individuals, 11 males and two females. Assuming that the individuals affected with hypomagnesemia shared a chromosomal region inherited from a common ancestor, we used a DNA pooling strategy in a genome-wide search for loci which show homozygosity for shared alleles in affected individuals. DNA samples from affected individuals within a single kindred were pooled and used as the template for PCR amplification of short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected siblings and parents were used as controls. A shift towards homozygosity was observed in the affected DNA pool compared with the control pools with D9S301 (GATA7D12). Genotyping of individual DNA samples with D9S301 and several flanking markers confirmed linkage to chromosome 9 with maximum LOD scores of 3.4 (theta = 0.05), 3.7 (theta = 0) and 2.3 (theta = 0) for the three families. We have identified a 14 cM interval on chromosome 9 (9q12-9q22.2), flanked by proximal marker D9S1874 and distal marker D9S1807, within which all affected individuals from the three kindreds are homozygous for a shared haplotype. The disease segregates with a common affected haplotype in the three families, suggesting that hypomagnesemia is caused by a common ancestral mutation in these families. Although HSH has been previously reported to be X linked, these linkage data demonstrate that the disorder is an autosomal recessive disease in these kindreds. Mapping of a chromosomal breakpoint in a somatic cell line established from a patient with HSH and a balanced X;9 translocation placed the chromosomal breakpoint in a 500 kb region flanked by D9S1844 and D9S273. Identification of the gene responsible for hypomagnesemia will provide insight into the regulation of this essential cation.

Asunto(s)

Cromosomas Humanos Par 9/genética , Marcadores Genéticos , Magnesio/sangre , Errores Innatos del Metabolismo/genética , Translocación Genética , Árabes , Técnicas de Cultivo de Célula , Mapeo Cromosómico , Femenino , Ligamiento Genético , Humanos , Lactante , Recién Nacido , Masculino , Linaje , Cromosoma X/genética

RESUMEN

Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of severe inherited childhood deafness. We present the linkage analysis of two inbred Bedouin kindreds from Israel that are affected with ARNSHL. A rapid genomewide screen for markers linked to the disease was performed by using pooled DNA samples. This screen revealed evidence for linkage with markers D9S922 and D9S301 on chromosome 9q. Genotyping of individuals from both kindreds confirmed linkage to chromosome 9q and a maximum combined LOD score of 26.2 (recombination fraction [theta] .025) with marker D9S927. The disease locus was mapped to a 1.6-cM region of chromosome 9ql3-q2l, between markers D9S15 and D9S927. The disease segregates with a common haplotype in the two kindreds, at markers D9S927, D9S175, and D9S284 in the linked interval, supporting the hypothesis that both kindreds inherited the deafness gene from a common ancestor. Although this nonsyndromic-hearing-loss (NSHL) locus maps to the same cytogenetic interval as DFNB7, it does not overlap the currently defined DFNB7 interval and may represent (1) a novel form of NSHL in close proximity to DFNB7 or (2) a relocalization of the DFNB7 interval to a region telomeric to its reported location. This study further demonstrates that DNA pooling is an effective means of quickly identifying regions of linkage in inbred families with heterogeneous autosomal recessive disorders.

Asunto(s)

Árabes/genética , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Cromosomas Humanos Par 9 , Genes Recesivos , Pérdida Auditiva Sensorineural/genética , Mapeo Cromosómico , Consanguinidad , Femenino , Marcadores Genéticos , Pérdida Auditiva Sensorineural/congénito , Pérdida Auditiva Sensorineural/etnología , Humanos , Endogamia , Israel/etnología , Escala de Lod , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Secuencias Repetitivas de Ácidos Nucleicos

RESUMEN

Bardet-Biedl syndrome (BBS) is an autosomal-recessive disorder of mental retardation, obesity, retinal dystrophy, polydactyly, and hypogenitalism. Renal and cardiac abnormalities are also frequent in this disorder. Previous clinical suggestions of heterogeneity of BBS were confirmed recently by the identification of four different chromosome loci linked to the disease. In this study we compared clinical manifestations of the syndrome in patients from 3 unrelated, extended Arab-Bedouin kindreds which were used for the linkage mapping of the BBS loci to chromosomes 3, 15, and 16. The observed differences included the limb distribution of the postaxial polydactyly and the extent and age-association of obesity. It appears that the chromosome 3 locus is associated with polydactyly of all four limbs, while polydactyly of the chromosome 15 type is mostly confined to the hands. On the other hand, the chromosome 15 type is associated with early-onset morbid obesity, while the chromosome 16 type appears to present the "leanest" form of BBS. Future cloning of the various BB genes will contribute to the understanding of the molecular basis of limb development and to the identification of human obesity-related genes.

Asunto(s)

Discapacidad Intelectual/genética , Obesidad/genética , Degeneración Retiniana/genética , Adolescente , Adulto , Árabes , Niño , Preescolar , Cromosomas Humanos Par 15/genética , Cromosomas Humanos Par 16/genética , Cromosomas Humanos Par 3/genética , Femenino , Ligamiento Genético , Genitales/anomalías , Humanos , Lactante , Masculino , Fenotipo , Polidactilia/genética , Síndrome

Asunto(s)

Consanguinidad , Sordera/genética , Ligamiento Genético , Árabes , Mapeo Cromosómico , Cromosomas Humanos Par 13 , Conexina 26 , Conexinas , Humanos , Israel , Escala de Lod , Linaje

RESUMEN

Bardet-Biedl syndrome is a heterogeneous autosomal recessive disorder characterized by obesity, mental retardation, polydactyly, retinitis pigmentosa and hypogonadism. Patients with this disorder also have a high incidence of hypertension, diabetes mellitus, and renal and cardiovascular anomalies. Three independent loci causing Bardet-Biedl syndrome have previously been reported. In this study, we we utilized a DNA pooling approach using DNA samples from a highly inbred Bedouin kindred to identify a new Bardet-Biedl syndrome locus on chromosome 15. The results further demonstrate the genetic heterogeneity of this disorder. In addition, the results demonstrate the efficiency of the DNA pooling approach for identifying recessive disease loci in highly inbred human populations.

Asunto(s)

Cromosomas Humanos Par 15 , ADN/genética , Obesidad/genética , Femenino , Homocigoto , Humanos , Hipogonadismo/genética , Discapacidad Intelectual/genética , Masculino , Linaje , Polidactilia/genética , Retinitis Pigmentosa/genética , Síndrome

RESUMEN

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by mental retardation, obesity, retinitis pigmentosa, polydactyly and hypogonadism. Individuals with this disorder also have an increased incidence of hypertension, diabetes mellitus, and renal and cardiac anomalies. We previously identified a locus on chromosome 16 causing this disorder, and provided evidence that Bardet-Biedl syndrome is heterogeneous. In this study, we identify another Bardet-Biedl syndrome locus on chromosome 3 and confirm the non-allelic heterogeneity of this disorder in Bedouin populations. In addition, we demonstrate the feasibility of using pooled DNA samples from members of large kindreds as an efficient approach to homozygosity mapping.

Asunto(s)

Mapeo Cromosómico , Cromosomas Humanos Par 3 , Ligamiento Genético , Síndrome de Laurence-Moon/genética , ADN/genética , Estudios de Evaluación como Asunto , Femenino , Homocigoto , Humanos , Lactante , Masculino , Linaje

RESUMEN

The Bardet-Biedl syndrome is an autosomal recessive disorder of polydactyly, obesity, tapetoretinal degeneration, mental retardation, hypogenitalism, and renal involvement. A high incidence of congenital and acquired heart disease was reported in the former "Laurence-Moon-Biedl-Bardet" syndrome. However, since the establishment of the Bardet-Biedl syndrome as a separate clinical entity, cardiac involvement has not been evaluated in this disorder. We have performed echocardiographic studies on 22 patients with the Bardet-Biedl syndrome from three extended, highly inbred Bedouin families. In addition to previously reported congenital heart defects we have observed hypertrophy of the interventricular septum and dilated cardiomyopathy. Our findings of cardiac involvement in 50% of the cases suggest that echocardiographic examination should be included in the clinical evaluation and follow-up of patients with Bardet-Biedl syndrome.

Asunto(s)

Cardiomiopatía Dilatada/genética , Ecocardiografía , Cardiopatías Congénitas/genética , Síndrome de Laurence-Moon/patología , Adolescente , Adulto , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/patología , Niño , Preescolar , Consanguinidad , Etnicidad/genética , Femenino , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/patología , Tabiques Cardíacos/patología , Humanos , Hipertrofia , Lactante , Israel , Riñón/anomalías , Riñón/diagnóstico por imagen , Síndrome de Laurence-Moon/genética , Masculino , Linaje , Distribución por Sexo

RESUMEN

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by mental retardation, obesity, retinitis pigmentosa, polydactyly and hypogonadism. Other findings include hypertension, diabetes mellitus and renal and cardiovascular anomalies. We have performed a genome-wide search for linkage in a large inbred Bedouin family. Pairwise analysis established linkage with the locus D16S408 with no recombination and a lod score of 4.2. A multilocus lod score of 5.3 was observed. By demonstrating homozygosity, in all affected individuals, for the same allele of marker D16S408, further support for linkage is found, and the utility of homozygosity mapping using inbred families is demonstrated. In a second family, linkage was excluded at this locus, suggesting non-allelic genetic heterogeneity in this disorder.

Asunto(s)

Cromosomas Humanos Par 16 , Discapacidad Intelectual/genética , Obesidad/genética , Retinitis Pigmentosa/genética , Mapeo Cromosómico , Femenino , Ligamiento Genético , Homocigoto , Humanos , Hipogonadismo/genética , Escala de Lod , Masculino , Linaje , Polidactilia/genética