X-linked Inheritance (X-link + inheritance)

Distribution by Scientific Domains

Selected Abstracts

Autosomal Dominant Inheritance of Centrotemporal Sharp Waves in Rolandic Epilepsy Families

EPILEPSIA, Issue 12 2007
Bhavna Bali
Summary Purpose: Centrotemporal sharp (CTS) waves, the electroencephalogram (EEG) hallmark of rolandic epilepsy, are found in approximately 4% of the childhood population. The inheritance of CTS is presumed autosomal dominant but this is controversial. Previous studies have varied considerably in methodology, especially in the control of bias and confounding. We aimed to test the hypothesis of autosomal dominant inheritance of CTS in a well-designed family segregation analysis study. Methods: Probands with rolandic epilepsy were collected through unambiguous single ascertainment. Siblings in the age range 4,16 years underwent sleep-deprived EEG; observations from those who remained awake were omitted. CTS were rated as present or absent by two independent observers blinded to the study hypothesis and subject identities. We computed the segregation ratio of CTS, corrected for ascertainment. We tested the segregation ratio estimate for consistency with dominant and recessive modes of inheritance, and compared the observed sex ratio of those affected with CTS for consistency with sex linkage. Results: Thirty siblings from 23 families underwent EEG examination. Twenty-three showed evidence of sleep in their EEG recordings. Eleven of 23 recordings demonstrated CTS, yielding a corrected segregation ratio of 0.48 (95% CI: 0.27,0.69). The male to female ratio of CTS affectedness was approximately equal. Conclusions: The segregation ratio of CTS in rolandic epilepsy families is consistent with a highly penetrant autosomal dominant inheritance, with equal sex ratio. Autosomal recessive and X-linked inheritance are rejected. The CTS locus might act in combination with one or more loci to produce the phenotype of rolandic epilepsy. [source]

Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype,phenotype correlations and impact on genetic counseling,,

HUMAN MUTATION, Issue 1 2007
Valérie Pelletier
Abstract X-linked forms of retinitis pigmentosa (RP) (XLRP) account for 10 to 20% of families with RP and are mainly accounted for by mutations in the RP2 or RP GTPase regulator (RPGR) genes. We report the screening of these genes in a cohort of 127 French family comprising: 1) 93 familial cases of RP suggesting X-linked inheritance, including 48 out of 93 families with expression in females but no male to male transmission; 2) seven male sibships of RP; 3) 25 sporadic male cases of RP; and 4) two cone dystrophies (COD). A total of 5 out of the 93 RP families excluded linkage to the RP2 and RP3 loci and were removed form the cohort. A total of 14 RP2 mutations, 12 of which are novel, were identified in 14 out of 88 familial cases of RP and 1 out of 25 sporadic male case (4%). In 13 out of 14 of the familial cases, no expression of the disease was noted in females, while in 1 out of 14 families one woman developed RP in the third decade. A total of 42 RPGR mutations, 26 of which were novel, were identified in 80 families, including: 69 out of 88 familial cases (78.4%); 2 out of 7 male sibship (28.6%); 8 out of 25 sporadic male cases (32.0%); and 1 out of 2 COD. No expression of the disease was noted in females in 41 out of 69 familial cases (59.4%), while at least one severely affected woman was recognized in 28 out of 69 families (40.6%). The frequency of RP2 and RPGR mutations in familial cases of RP suggestive of X-linked transmission are in accordance to that reported elsewhere (RP2: 15.9% vs. 6,20%; RPGR: 78.4% vs. 55,90%). Interestingly, about 30% of male sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations, confirming the pertinence of the genetic screening of XLRP genes in male patients affected with RP commencing in the first decade and leading to profound visual impairment before the age of 30 years. Hum Mutat 28(1), 81,91, 2007. © 2006 Wiley-Liss, Inc. [source]

Evaluation of an automated screening assay for von Willebrand Disease Type 2N

S. L. Taylor
Summary Evaluating the factor VIII (FVIII) binding activity of von Willebrand factor (VWF) is an important step in the diagnostic work-up of families affected by apparent mild haemophilia A. In von Willebrand's disease (VWD) type 2N (Normandy), mutations at the N-terminal end of the mature VWF subunit gene prevent the binding of FVIII. Individuals heterozygous for type 2N VWD are generally asymptomatic. Homozygotes and compound heterozygotes present with a clinical picture which mimics haemophilia A, with a markedly reduced FVIII : C activity and VWF within the normal range, but instead of exhibiting X-linked inheritance they show an autosomal recessive inheritance pattern. The distinction between haemophilia A and VWD type 2N has important implications for therapy and genetic counselling. We present a highly specific enzyme-linked immunosorbent assay screening method for the Normandy variant, which measures VWF : FVIII binding activity in parallel with VWF antigen, using monoclonal capture and detection antibodies. The assay is fully automated using a robotic microtitre plate processor, requiring minimal user intervention and providing the capacity to screen large numbers of patients. [source]

PCD and RP: X-linked inheritance of both disorders?

Maciej R. Krawczy, ski MD
A Caucasian, seven-generation family of Polish origin with apparently X-linked inheritance of coexisting retinitis pigmentosa (RP) and primary ciliary dyskinesia (PCD), with 14 identified males affected with RP and 14 obligate healthy female carriers, is presented. To our knowledge, four of the RP-affected males were diagnosed with PCD. The cases might imply the presence of one of the PCD loci, influencing neither laterality nor fertility, within the X-chromosome. Pediatr Pulmonol. © 2004 Wiley-Liss, Inc. [source]

Acute lymphoblastic leukemia in a patient with chronic granulomatous disease and a novel mutation in CYBB: First report

Baruch Wolach
Abstract We report for the first time a child with chronic granulomatous disease (CGD) who developed acute lymphoblastic leukemia (ALL). The diagnosis of CGD was made at the age of 4 months, by studies of his neutrophil functions. The superoxide production of the cells was negligible, as was the bactericidal activity. He was found to have a deficiency of the gp91phox subunit of the leukocyte NADPH oxidase, with the X-linked inheritance of the disease. DNA analysis revealed a C nucleotide insertion between C1028 and T1029. This insertion has not been described before and causes a frameshift and a premature stop codon at amino-acid position 347. The mother was found to be a carrier of this mutation. At the age of 16 months, the patient developed T-cell ALL. He was treated for 2 years, and today, 10 years since the diagnosis, he is disease-free. During the course of ALL and later, he suffered from recurrent severe pyogenic infections, but careful detection of the etiological agent and promptly instituted specific treatment resulted in his complete recovery. Although primary immune deficiencies have been reported to have an increased tendency to develop malignancies, until now there have been no reports of CGD patients with ALL. Am. J. Hematol. 80:50,54, 2005. © 2005 Wiley-Liss, Inc. [source]

Brief communication: Familial resemblance in digit ratio (2D:4D)

Martin Voracek
Abstract Familial resemblance in the second-to-fourth digit ratio (2D:4D), a proxy for prenatal androgen action, was studied in 1,260 individuals from 235 Austrian families. In agreement with findings from twin studies of 2D:4D, heritability estimates based on parent,child and full-sib dyad similarity indicated substantial genetic contributions to trait expression (57% for right hand, 48% for left hand 2D:4D). Because twin studies have found nonadditive genetic as well as shared environmental effects on 2D:4D to be negligible or nil, these family-based estimates in all likelihood reflect the narrow-sense (additive genetic) heritability of the trait. Directional (right-minus-left) asymmetry in 2D:4D was only weakly heritable (6%). The pattern of same-sex and different-sex parent,child and full-sib correlations yielded no evidence for X-linked inheritance. This is surprising, considering evidence for associations of male 2D:4D with sensitivity to testosterone (functional variants of the X-linked androgen receptor gene). 2D:4D was particularly strongly heritable through male lines (father,son and brother,brother correlations), thus raising the possibility that Y-linked genes (such as the sex-determining region SRY) might influence 2D:4D expression. Am J Phys Anthropol, 2009. © 2009 Wiley-Liss, Inc. [source]

DNA sequence analysis for structure/function and mutation studies in Becker muscular dystrophy

SA Hamed
We systematically screened the whole coding region of 18 male muscular dystrophy patients whose clinical, histological and laboratory findings suggest Becker muscular dystrophy (present but abnormal dystrophin). No systematic mutation study of a cohort of patients with dystrophin of normal quality but abnormal quantity has been published. The complete coding sequence of the dystrophin gene (11 kb) of each patient was subjected to an automated sequence analysis by using muscle biopsy RNA; 535 bp of the gene promoter and 5,UTR were likewise sequenced. We identified seven disease-causing mutations (40%). Six were novel, including missense, nonsense, small deletion and splice site mutations. Sixty percent (11/18) of patients with decreased quantities of normal molecular weight dystrophin showed no mutation, but most of them had a family history highly suggestive of X-linked inheritance, suggesting transcription or translational deleterious affection, i.e. outside what was screened. Quantitative multiplex fluorescence polymerase chain studies of mutation-negative patients showed normal levels of dystrophin mRNA. In three patients, there was some reduction of the transcript suggesting a deleterious undetected gene change resulted in the reduction of RNA levels. Our data address important structure/function and genotype/phenotype correlations and it suggests that dystrophin protein studies must be interpreted with caution in deletion-negative male muscular dystrophy patients. [source]