Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Consanguinity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,261 records · Page 70Linked to original sources
PubMed1994

Autosomal recessive hereditary sensory neuropathy with spastic paraplegia.

Five patients are described with a progressive sensory neuropathy in association with a spastic paraplegia and a mutilating lower limb acropathy. Disease onset was in childhood. Two pairs of siblings were both the offspring of normal consanguinous parents, suggesting autosomal recessive inheritance. The fifth case was sporadic; her parents were normal and non-consanguinous. Nerve biopsy in three patients showed an axonopathy with a loss of myelinated nerve fibres of all diameters and also of unmyelinated axons. In combination with the previous report by Cavanagh et al. (Brain 1979; 102: 79-94), the present patients establish the existence of an autosomal recessive form of hereditary sensory neuropathy with spastic paraplegia. There have been previous descriptions of a dominantly inherited form.

Adolescent↗
PubMed2002

Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1).

Lipoid proteinosis (LP), also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease (OMIM 247100) is a rare, autosomal recessive disorder typified by generalized thickening of skin, mucosae and certain viscera. Classical features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. Histologically, there is widespread deposition of hyaline (glycoprotein) material and disruption/reduplication of basement membrane. The aetiology of LP is currently unknown. Using DNA from three affected siblings in a consanguineous Saudi Arabian family we performed genome-wide linkage and mapped the disorder to 1q21 (marker D1S498) with a two-point LOD score of 3.45 at theta = 0. A further 28 affected individuals from five other unrelated consanguineous family groups from different geographical regions also showed complete linkage and resulted in a maximum two-point LOD score of 21.85 at theta = 0. Using available markers in the interval between D1S442 and D1S305, the observed recombinants placed the gene in a 2.3 cM critical interval between D1S2344 and D1S2343 (Marshfield genetic map) corresponding to an approximately 6.5 Mb region on the UCSC physical map. Using a candidate gene approach (comparison of control versus LP gene expression in cultured fibroblasts) and subsequent direct sequencing of genomic DNA, we identified six different homozygous loss-of-function mutations in the extracellular matrix protein 1 gene (ECM1). Although the precise function of ECM1 is not known, our findings provide the first clinical indication of its relevance to skin adhesion, epidermal differentiation, wound healing, scarring, angiogenesis/angiopathy and basement membrane physiology, as well as defining the molecular basis of this inherited disorder.

Blood Vessels↗
PubMed1996

Mapping of a second locus for lamellar ichthyosis to chromosome 2q33-35.

Lamellar ichthyosis (LI) is an inherited autosomal recessive disorder of cornification. It was recently demonstrated to result from deleterious mutations in the transglutaminase 1 (TGM1) gene. However, the disease was shown to be genetically heterogeneous, since some families were found to be unlinked to TGM1. Homozygosity mapping on three consanguinous families originating from Morocco shows (i) absence of linkage with TGM1 and other regions of the genome containing genes involved in cornification, and (ii) location of a second disease-causing gene on chromosome 2q33-35. A maximum two-point lodscore of 7.60 was obtained with D2S157 for theta = 0. The analysis of recombination events places the gene within a 7-8 cM interval. Additional consanguinous pedigrees were also demonstrated to be unlinked both to TGM1 and to 2q33-35, suggesting the existence of at least a third disease-causing gene.

Chromosome Mapping↗
PubMed2003

Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome.

Kindler syndrome is a rare autosomal-recessive genodermatosis characterized by bullous poikiloderma with photosensitivity. We report the localization to chromosome 20p12.3 by homozygosity mapping and the identification of a new gene, which we propose to name kindlerin. We found four different homozygous mutations in four consanguineous families from North Africa and Senegal; three are expected to lead to premature stop codons and truncated proteins and the fourth involves a splice site. We were unable to identify a mutation in kindlerin in a fifth consanguineous family from Algeria with a similar phenotype and in which the patient was homozygous for the markers in the 20p12.3 interval. The kindlerin protein contains several domains which are shared by a diverse group of peripheral membrane proteins that function as membrane-cytoskeleton linkers: two regions homologous to band 4.1 domain of which one includes a FERM domain with a NPKY sequence motif, and a third region with a PH or pleckstrin homology domain. Kindlerin might be involved in the bidirectional signaling between integrin molecules in the membrane and the cytoskeleton, and could be involved in cell adhesion processes via integrin signaling.

Adolescent↗
PubMed2005

Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive disorder characterized by hyperactive phagocytes and defects in natural killer cell function. It has been shown previously that mutations in the perforin 1 gene (PRF1) and in UNC13D are associated with FHL2 and FHL3, respectively, indicating genetic heterogeneity. We performed genome-wide homozygosity mapping in a large consanguineous Kurdish kindred with five children affected with FHL. Linkage to a 10 cM region on chromosome 6q24 between D6S1569 and D6S960 defined a novel FHL locus. By screening positional candidate genes, we identified a homozygous deletion of 5 bp in the syntaxin 11 gene (STX11) in this family. We could demonstrate that syntaxin 11 protein was absent in the mononuclear cell fraction of patients with the homozygous 5 bp deletion. In addition to this family, we found homozygous mutations in STX11 in five consanguineous Turkish/Kurdish FHL kindreds including two families with the 5 bp deletion, one family with a large 19.2 kb genomic deletion spanning the entire coding region of STX11 (exon 2) and two families with a nonsense mutation that leads to a premature stop codon in the C-terminal end of the protein. As both STX11 and UNC13D are involved in vesicle trafficking and membrane fusion, we conclude that, besides mutations in perforin 1, defects in the endocytotic or the exocytotic pathway may be a common mechanism in FHL.

Chromosomes, Human, Pair 6↗
PubMed2005

Autosomal-recessive Charcot-Marie-Tooth diseases.

In certain countries around the Mediterranean basin such as Algeria, which have a high prevalence of consanguineous marriages, autosomal-recessive (AR) inheritance may account for more than 50% of all forms of Charcot-Marie-Tooth (CMT) disease. Like with the dominant forms, it is usual to differentiate the demyelinating forms (CMT 4 corresponding to autosomal-recessive CMT 1 [AR-CMT 1] from the axonal forms [AR-CMT 2]). Genetic analysis of large families with recessive transmission has uncovered novel CMT genotypes (genes: GDAP 1, MTMR 2, MTMR 13, KIAA1985, NDGR1, periaxi, lamin). The clinical and especially the histologic phenotypes often indicate that a specific gene is implicated. We present and discuss microscopic lesions seen on nerve biopsies from patients in a number of consanguineous Algerian families, and we outline the characteristic lesions that would prompt a search for mutations in genes such as MTMR 2, MTMR 13, KIAA1985, periaxin for CMT 4, and lamin for AR-CMT 2. Like with the dominant forms, there are undoubtedly many more mutations of other genes to be discovered.

Charcot-Marie-Tooth Disease↗
PubMed2004

Familial Diamond-Blackfan anemia. Case reports and a review of the related literature.

We present the case of three sisters with Diamond-Blackfan anemia (DBA) from a consanguineous marriage. These sisters presented within the first 2 months of age with anemia without hepatosplenomegaly together with complete blood count and bone marrow pictures compatible with the diagnosis of DBA syndrome. They were given blood transfusions and then started on prednisolone 2 mg/kg/day in divided doses, tapering the dose to a minimum to keep Hb around 90 g/l. DBA in these three sisters from a consanguineous marriage clearly illustrates the autosomal recessive mode of inheritance. The importance of early diagnosis and management with steroid is highlighted along with the need for consideration of other modalities of treatment in those cases not responding to steroid therapy.

Anemia, Diamond-Blackfan↗
PubMed2000

Raine dysplasia: a Brazilian case with a mild radiological involvement.

We report a preterm male infant, the first child of a young consanguineous couple, whose physical examination revealed craniofacial disproportion with microcephaly, wide fontanelles, exophthalmos, low nasal root and hypoplastic nose, long philtrum, small mouth, high arched and narrow palate, micrognathia, dysplastic, low-set and rounded ears, short neck and, arthrogryposis. Postmortem findings included hypoplastic lungs. Radiological examinations showed mild and localized increased of bone density in the cranial vault and skull base and facial bones and undermodelled in the long bones. The above findings are characteristics of Raine dysplasia but the case reported here presents a mild bone involvement with only a localized bone sclerosis and absence of prenatal fractures. We discuss the possibility that this case represents an allelic mutation of the Raine gene. The consanguinity of the parents reinforces the hypothesis of autosomal recessive inheritance for this entity.

Abnormalities, Multiple↗
PubMed2002

Hemifacial microsomia, external auditory canal atresia, deafness and Mullerian anomalies associated with acro-osteolysis: a new autosomal recessive syndrome?

We report the combination of hemifacial microsomia, external auditory canal atresia, deafness and acro-osteolysis in several members of a highly consanguineous Asian family. In addition Mullerian anomalies have been found in two female members of the family. The external auditory canal stenosis and Mullerian anomalies in this family are similar to those reported by Winter et al. [(1968) J Pediatr 72 : 88-93] and overlap with those found in Goldenhar syndrome and Mullerian duct/renal aplasia/cervicothoracic somite dysplasia (MURCS), CHARGE and VATER associations. However, to the authors' knowledge, acro-osteolysis has not been reported in patients with any of these conditions. Overall, the findings in this family appear to be unique and the presence of consanguinity suggests an autosomal recessive condition with variable expression.

Abnormalities, Multiple↗
PubMed2005

Primary congenital glaucoma presenting within the first three months of life in a Bedouin population: prognostic factors.

OBJECTIVES: To analyze the final outcome of surgery in Arab-Bedouin children with primary congenital glaucoma (PCG) presenting within the first three months of life, and to search for prognostic factors for success. DESIGN: Retrospective study of all cases with follow-up of at least 24 months. PATIENTS: Twenty-five Arab-Bedouin children (45 eyes) with PCG presenting within the first three months of life who underwent surgical procedures at the Soroka University Medical Center from January 1988 to December 1998. METHODS: Patient's age, family history, main presenting features, data from examinations under anesthesia, including intraocular pressure (IOP), horizontal corneal diameter, and cup/disc (c/d) ratio, and the type of surgery performed were reviewed. MAIN OUTCOME MEASURES: Success of the first operation, defined as final IOP < 21 mm Hg achieved after only one surgical procedure without anti-glaucoma medication, and final outcome, defined as good when IOP was < 21 mm Hg and > 5 mm Hg at the end of a 24-month follow-up period without anti-glaucoma medication, irrespective of the number of procedures performed. RESULTS: At presentation mean IOP was 36.2 +/- 8.0 mm Hg, corneal diameter was 12.62 +/- 0.98 mm, and c/d ratio was 0.41 +/- 0.16. The mean age at first operation was 17 +/- 20 days, and median of 5 days. The mean follow-up period was 37.4 +/- 25.4 months. The success of the first operation performed was not related to the type of operation (P = 0.22), gender (P = 0.47), consanguinity (P = 1.0), family history (P = 0.12), clinical presentation (P = 0.81), or age at first operation (P = 0.38). Eyes with high initial IOP and greater c/d ratio were at a significantly higher risk for failure (P = 0.05, P = 0.04, respectively). A final outcome of IOP under 21 mm Hg and above 5 mm Hg was achieved in 39 eyes (86.5%). There was no statistical association between final outcome and the type of first surgical procedure performed, gender, consanguinity, clinical presentation, and age at first operation. Cases with no family history had a significantly better final outcome (P = 0.05). In multivariate analysis only initial IOP showed borderline significance as an independent risk factor for final outcome (P = 0.06). CONCLUSIONS: Initial high IOP and higher c/d ratio were found to be predictive factors for failure of the first procedure. Final outcome was significantly better in cases with no family history, yet initial IOP was the only independent predictive factor for failure at the final outcome in a multivariate model. Findings of this type have not been previously reported, and they may constitute an important tool in predicting the treatment outcome of very young children with PCG.

Arabs↗
PubMed2006

Mietens-Weber syndrome: two new patients and a review.

In 1966, Mietens and Weber reported four out of six siblings from a consanguineous couple with growth failure, dislocation of the head of the radii, bilateral flexion contracture of the elbows, short ulnae and radii, bilateral corneal opacities, horizontal and rotational nystagmus, strabismus, small, pointed nose and mild to moderate mental retardation. Since then, only three other cases have been reported. We report on two new cases, a pair of female twins aged 9 years. The patients were born after an uneventful, normal pregnancy, to young and non-consanguineous parents. After birth, physical findings included horizontal nystagmus and dislocation of both elbows because of abnormally short radii and ulnae in both twins. Further clinical examinations showed moderate psychomotor delay with marked language compromise. Karyotypes were normal in both girls. A review of the literature reveals that the Mietens-Weber syndrome is an uncommon disorder with a probable autosomal recessive pattern of inheritance. To our best knowledge, including the two cases reported here, only nine cases have been observed so far. The finding of congenital nystagmus and radii dislocation in a patient with mental retardation is probably nonrandom and is highly suggestive of Mietens-Weber syndrome.

Abnormalities, Multiple↗
PubMed2004

Localization of a novel locus for hereditary nail dysplasia to chromosome 17q25.1-17q25.3.

We report on a six-generation Pakistani consanguineous family with autosomal recessive transmission of a form of hereditary nail dysplasia. Affected individuals presented with onycholysis of fingernails and anonychia of toenails. Associated abnormalities of ectodermal appendages were not observed in any of the affected individuals. Linkage has been established to chromosome 17q. A maximum multipoint analysis logarithm of the odds ratio score of 4.85 was obtained at marker D17S1301. Due to the consanguineous nature of this kindred, the gene for nail dysplasia is probably contained within a 5.0-cM (3 MB on the sequence-based physical map) region of homozygosity flanked by markers D17S1807 and D17S937.

Chromosomes, Human, Pair 17↗
PubMed2006

Ectodermal dysplasia of hair and nail type: mapping of a novel locus to chromosome 17p12-q21.2.

BACKGROUND: Ectodermal dysplasias (EDs) describe a large and complex group of disorders characterized by abnormal development of the skin and appendages (hair, nails, teeth and sweat glands). Of the approximately 200 different EDs, about 30 have been studied at the molecular level. In an effort to understand the molecular bases of ED of hair and nail type, we studied a Pakistani consanguineous family with multiple affected individuals. OBJECTIVES: To localize the gene responsible for the autosomal recessive form of ED of hair and nail type. METHODS: Genotyping of nine members of the family, including five affected and four normal individuals was performed using microsatellite markers mapping to candidate regions, harbouring genes involved in related phenotypes. Five epithelial keratin genes located in the candidate region were sequenced to identify the pathogenic mutation. RESULTS: We mapped the disease locus to a 24.2-cM interval flanked by markers D17S839 and D17S1299 on chromosome 17p12-q21.2 (Z(max) = 4.4). DNA sequencing of five epithelial keratin candidate genes, present in the disease locus, did not reveal any pathogenic mutation in the affected individuals. CONCLUSIONS: The gene for ED of hair and nail type has been mapped to chromosome 17p12-q21.2 in a Pakistani consanguineous family. Failure to detect mutations in epithelial keratin genes suggests that the mutation may lie either in regulatory regions of one of the epithelial keratin genes or in another unknown gene, located in the linkage interval, with a possible role in the development of ectodermal appendages.

Chromosome Mapping↗
PubMed1995

HLA antigens in Omani patients with vitiligo.

Fifty native Omanis with vitiligo were studied to compare the incidence of HLA ABC and DR antigens with a control population. HLA Bw6 was found in 82% of patients compared with 49% controls (Pc = 0.0009 RR = 4.56) and HLA DR7 occurred in 40% of patients and 9% in controls (Pc = 0.00075 RR = 6.17). HLA DR7 was significantly increased in those patients with acrofacial, compared to focal disease (57% vs. 24% P = 0.038). Sixty-six per cent of the patients in this study had parents who were consanguineous and a positive family history was only found in this group with an incidence of 32%. HLA Bw4 segregated 100% with patients with a positive family history compared with 48% in consanguineous patients without a positive family history (Pc = 0.011 RR = 23). Vitiligo appears to be associated with different HLA antigens in different ethnic groups.

Female↗
PubMed1991

Why do UK-born Pakistani babies have high perinatal and neonatal mortality rates?

A prospective study of 4934 babies of different ethnic groups has confirmed the high perinatal mortality rate for Pakistanis and has shown that this was not due to a reluctance to terminate a fetus who is known to be seriously malformed. The major cause of early mortality was a high rate of lethal malformations, which occurred in about 1 in 100 Pakistani babies and which accounted for about half of their perinatal mortality. Many of these were autosomal recessive and occurred only in the offspring of consanguineous parents. However, there was also an excess of lethal cardiac malformations which were not associated with parental consanguinity. The remainder of the excess perinatal mortality was probably due to socio-economic factors. These causes are partly amenable to preventive measures, such as the referral of Pakistani women for expert ultrasonography at 18 to 20 weeks of pregnancy.

Cause of Death↗
PubMed1985

Mycobacterium leprae-induced alterations in macrophage Fc receptor expression and monocyte-lymphocyte interaction in familial contacts of leprosy patients.

Macrophage Fc receptor expression and monocyte-lymphocyte interaction in the presence of Mycobacterium leprae were examined in familial contacts of leprosy patients. Defective M phi functions similar to those of borderline and lepromatous patients could be observed in approximately 71% of consanguineous contacts and 43% of spouses of index patients. Although the values in the latter group were markedly lower than those of the consanguineous contacts, they tended to be higher than those of normal individuals (20%). These in vitro M phi functions were independent of age, sex, and age at onset of exposure and were only weakly associated with duration of exposure. The outcome of the monocyte-lymphocyte interaction test paralleled to a large extent the in vivo Mitsuda lepromin response. Four contacts with defective M phi functions also showed signs of leprosy. The value of these in vitro tests as markers of 'susceptibility' could therefore prove significant.

Age Factors↗
PubMed1982

Ivemark syndrome in siblings.

A family in which two brothers have the Ivemark syndrome is reported, thus bringing to eight the total number of families reported with multiple affected siblings. Study of 4059 autopsies, performed over 21 years at a major pediatric referral hospital, identified 32 cases of Ivemark syndrome. All were isolated occurrences in the families. One of six families which provided complete pedigree information was found to be consanguineous. This brings to four the number of reported consanguineous families with Ivemark syndrome. The male excess of affected with Ivemark syndrome is found both for the families with multiple affected siblings and for autopsy-identified cases. These data suggest a recessive inheritance of Ivemark syndrome with male predisposition.

Abnormalities, Multiple↗
PubMed1986

The acrocallosal syndrome in sisters.

Two sisters born to non-consanguineous healthy parents are described who present the following abnormalities: macrocephalus, prominent forehead, hypertelorism, absence of the corpus callosum, inguinal hernias, duplication of hallucal phalanges and severe mental retardation. The older sister in addition had cleft palate, while only the younger had a supratentorial cyst between cerebrum and cerebellum and epileptic fits. After 6 sporadic cases, this is the first instance of siblings with the acrocallosal syndrome. This observation and definite and possible parental consanguinity in two further patients suggest that this syndrome might be recessively inherited.

Abnormalities, Multiple↗