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T Lukusa

Publications and source records attributed to T Lukusa.

At least 19 recordsLinked to original sources
PubMed2005

De novo deletion 7q36 resulting from a distal 7q/8q translocation: phenotypic expression and comparison to the literature.

We report on a 6-year-old male patient with de novo 7q36 deletion and 8q24.3 duplication diagnosed by combining traditional G-banding and FISH studies. His clinical history was remarkable for pre- and postnatal growth retardation, neonatal feeding problems and developmental/mental retardation with non-verbal communication. He presented microcephaly, large ears, narrow palpebral fissures with blepharoptosis, epicanthic folds, large depressed nasal bridge, bulbous nasal tip, right cryptorchidism and delayed bone age on X-rays. There was no evidence of holoprosencephaly (HPE) or sacral agenesis sequence. By using in FISH analysis a series of YACs linearly ordered along the 7q36 region, the precise breakpoint on 7q36 was found to be within the target region of the YAC 742G8, a YAC that appeared to be only partially deleted. Clinical and chromosomal findings in this patient are compared to those previously recorded in similarly investigated patients from the literature with terminal 7q deletion.

Carrier Proteins↗
PubMed2004

Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder.

Fine mapping of deletion regions in autistic patients represents a valuable screening tool for identifying candidate genes for autism. A number of studies have ascertained associations between autism and terminal 2q deletion with the breakpoint within 2q37. Here we describe a 12-year-old female patient with terminal 2q37.3 cryptic deletion and autistic behaviour. Her clinical features included hypotonia and feeding difficulties during infancy, coarse face with notably prominent forehead, prominent eyebrows, broad flat nasal bridge and round cheeks, small hands and feet with bilateral brachymetaphalangism, proximal implantation of the thumbs and short toenails, mild mental retardation and autistic behaviour. Recorded autistic features included early lack of eye contact and, during infancy, little social interactions, propensity to be stereotypically busy and to get anxious. In order to more closely delineate the linkage region for autism within 2q37, the findings in this patient were combined to those in 2 previously reported siblings with a well documented 2q37.3 deletion, but without autistic disorder. The exact size of the deleted segment was determined by mapping the deleted region in each group with a series of specific BAC clones linearly ordered on the 2q37 region. The deletion in the autistic patient appeared to be larger [breakpoint flanked by more centromeric clones RP11-680016 (236.9 Mb) and 201F21 (237.4 Mb)] than in the non autistic siblings [more telomeric clones RP11-205L13 (237.8 Mb) and 346114 (238.2 Mb)], revealing a distance of maximum 1.3 Mb between the breakpoints. Accordingly, the extent of the candidate region for susceptibility genes for autism on distal 2q is reduced to maximum 1.3 Mb. Comparison with another well documented autistic patient from the literature results in the same conclusion. These findings represent thus a further step towards identifying genes predisposing to autism.

Abnormalities, Multiple↗
PubMed2003

Partial monosomy 11q and trisomy 12q: variable expression in two siblings.

Clinical and cytogenetical findings are reported and discussed on two siblings with discordant phenotypes despite having both a terminal 11q deletion and a distal 12q duplication resulting from an unbalanced segregation of a balanced translocation t(11:12)(q23:q24.1) mat. The oldest child, a girl, is the index patient. Her clinical features include intrauterine and postnatal growth retardation, fetal distress, mild hypotonia, early feeding difficulties, moderate developmental delay, especially in language acquisition, a velopharyngeal insufficiency with repeated otorhinopharyngeal infections, facial dysmorphism, heart ventricular septal defect, and abnormal hyperactive behaviour with sometimes autistic tendencies. The facial dysmorphic features notably consist of microcephaly, hypertelorism, large palpebral fissures, large eyes with alternant divergent strabismus, long eyelashes, a long and broad nasal bridge, a short "crested" nose with salient tip, a fishmouth with large spaces between teeth and flat palate, retrognathism, large ears and multiple dimples. The second affected child is a boy showing low birthweight, moderate developmental retardation with mainly no active language at 32 months, behaviour abnormalities with an autistic tendency, and no major physical anomalies apart from a slight facial hypotonia with often open mouth, dimples on the shoulders and right cryptorchidism. The authors stress the variable clinical expression of the chromosomal imbalance in this family resulting in low birthweight, developmental delay, abnormal behaviour, but different degrees of physical features and dysmorphism. The possible contribution of each of the two aneusomies to the phenotype is discussed.

Child↗
PubMed2002

Pericentric inversion with partial 7(q35-->qter) duplication and 7pter deletion: diagnosis by cytogenetic and fish analysis in a 29-year-old male patient.

We report on a 29-year-old male patient with an inverted 7(q35-qter) duplication diagnosed by combining cytogenetic and FISH studies. Traditional G-banding detected an abnormally long chromosome 7 which was further demonstrated to be entirely of chromosome 7 origin by using fluorescent whole chromosome 7 painting. The presence within the additional segment of a signal for 7q36 region (Williams control probe) and the absence of signals for 7q33 (Y938G5 probe) and 7q34 (Y815G5 probe) regions indicated that the breakpoint for this rearrangement was distal to 7q34 and proximal to 7q36. A distal 7p22 deletion was confirmed by the absence of signal for the 7p subtelomeric probe. Apart from kyphosis, developmental/mental retardation and abnormal ears, the clinical features of the present patient, who is the oldest individual ever reported with this duplication/deletion, were not typical for partial 7q trisomy syndrome. A review of the cases reported with 7(q35-qter) duplication is made and shows important clinical variability but constantly normal pre- and postnatal growth, a feature which can therefore be confirmed as distinctive of distal 7q trisomy syndrome.

Abnormalities, Multiple↗
PubMed2002

Small terminal 10q26 deletion in a male patient with Noonan-like stigmata: diagnosis by cytogenetic and FISH analysis.

A male patient is reported with terminal 10q26 deletion, developmental retardation, special behaviour, and multiple clinical anomalies including hypotonia, short stature of postnatal onset, short webbed neck, craniofacial dysmorphism, pectus excavatum with widely spaced small nipples, cryptorchidism with scrotal hypoplasia, limb and musculoskeletal anomalies. The facial dysmorphism mainly consisted of trigonocephaly, a long, triangular and asymmetrical face, hypertelorism with pseudoepicanthus, broad nasal bridge, high-arched palate, retrognathia, low-set dysplastic auricles and, on ophthalmologic examination, strabismus, astigmatism and myopia. Some of these clinical stigmata were suggesting the diagnosis of Noonan syndrome. The extremities showed special features including shortening of proximal limbs, brachydactyly with syndactyly of toes II-III and left fingers III-IV, hypoplastic toenails and joint abnormalities. A diastasis of abdominal muscles was noted and, on X-rays a thoracic scoliosis and bilateral coxa valga were evidenced. Analyses of G- and T-banded chromosomes complemented by FISH analyses using different subtelomere probes detected a terminal 10q26 deletion. Subsequent FISH studies using different probes of the 10q26 region were performed in an attempt to closely define the breakpoint and the extent of the deletion and, thereby, to allow karyotype/phenotype comparison between this patient and a previously reported case with an apparently similar 10q26 deletion.

Chromosome Deletion↗
PubMed2001

Terminal 6q25.3 deletion and abnormal behaviour.

A 10-year-old mentally retarded boy with terminal 6q25 deletion, dysmorphism and striking abnormal behaviour is reported. The main abnormal physical features recorded at different ages consisted of hydrocephalus, axial hypotonia, absence of spontaneous prehension, long face, synophris, hypertelorism with epicanthic folds, internal alternating strabismus, retinal abnormalities with macular degeneration, beaked nose, long philtrum, high-arched palate, lumbar spina bifida, right paravertebral dimple at the upper sacral region, prominent coccyx, broad thumbs and great toes, fetal pads and cryptorchidism. The special behavioural difficulties were made of restlessness, hyperactivity, obsessive compulsive reactions with a self-injurious tendency and episodes of apparently voluntary vomiting crisis concomitant with stress periods. A review of the available literature strongly suggests that individuals with small chromosomal deletions are at high risk of developing behavioural problems.

Abnormalities, Multiple↗
PubMed2000

Dicentric chromosome 9 due to tandem duplication of the 9p11-q13 region: unusual chromosome 9 variant.

We report on a 31-year-old mentally retarded woman with minor facial anomalies and a heteromorphic chromosome 9 with tandem duplication of the 9p11-q13 pericentromeric region. To the best of our knowledge, this is the first report of tandem duplication of this region. An identical chromosome 9 morphology was found in the healthy and phenotypically normal sister of the proposita. The usefulness of double-color FISH techniques and the presumed mechanism accounting for the origin of the chromosomal anomaly and for the phenotypic discordance observed between the two sisters are discussed.

Adult↗
PubMed2000

Pure distal monosomy 10q26 in a patient displaying clinical features of Prader-Willi syndrome during infancy and distinct behavioural phenotype in adolescence.

A male patient is reported with terminal 10q26 deletion and clinical findings suggesting Prader-Willi syndrome during the infancy. These findings included decreased fetal movements, neonatal hypotonia, need for tube feeding, characteristic facial dysmorphism with dolichocephaly, narrow bifrontal diameter, almond-shaped eyes and epicanthus, hypogenitalism and developmental retardation. However, during the further evolution there was neither hyperphagia nor obesity and chromosomal and molecular investigations failed to confirm the diagnosis of Prader-Willi syndrome. Special behavioural abnormalities became evident with notably hyperactivity, hyperkinesis and destructive tendency. Finally, at the age of 17 years high resolution chromosome studies revealed a terminal 10q26.3 deletion. A review of the literature is made on previously reported patients with either a Prader-Willi-like syndrome or a terminal 10q deletion with behavioural problems.

Adolescent↗
PubMed1999

Mild dysmorphic signs in two male sibs with partial trisomy 2q32.1-->q35 due to maternal ins(14;2) translocation.

We report two male sibs with minor congenital anomalies and moderate to severe developmental delay who are trisomic for the interstitial 2q32.1-->q35 segment. The partial 2q duplication derived from a maternal balanced insertion translocation, 46,XX,dir ins (14;2)(q22;q32.1q35). To the best of our knowledge, no similar case observation has been previously published.

Abnormalities, Multiple↗
PubMed1999

A 3p deletion syndrome in a child with both del(3)(p25-->pter) and dup(17)(q23-->qter).

A child with monosomy for the distal part of the short arm of chromosome 3 (3p25-->pter) and trisomy for the terminal portion of the long arm of chromosome 17 (17q23-->qter) is presented. This unbalanced karyotype was derived from a balanced reciprocal 3p/17q translocation in the phenotypically normal mother. Main clinical features in the proband included growth and mental retardation, hypotonia, hirsutism, micro/brachycephaly, triangular face, synophris, broad and full nose, long philtrum, narrow upper lip, low set, posteriorly turned ears, anteriorly placed anus and congenital heart defect (Tetralogy of Fallot). Most of these clinical manifestations have been constantly reported in previous cases with terminal 3p deletion.

Child↗
PubMed1999

Proximal trisomy 13q and distal monosomy 8p in a dysmorphic and mentally retarded patient with an isodicentric chromosome 13q and a 13q/8p translocation chromosome.

A 40 year-old dysmorphic and mentally retarded female is reported with a de novo unbalanced chromosomal rearrangement (karyotype: 46,XX,der(8)t(8;13)(p23;q123),idic(13)(pter-->q123: q123-->pter) resulting in an isodicentric chromosome 13 and a double aneusomy including partial trisomy 13 (13pter-q123) and distal monosomy 8p (8pter-p23). The main clinical findings consist of developmental/mental retardation, behavioural disturbances and minor congenital defects, not consistent with the clinical pattern of either of the two aneusomies. A mechanism for the chromosome rearrangement is proposed and the absence of specific physical findings in the present patient is discussed in the light of the available literature data.

Abnormalities, Multiple↗
PubMed1998

Syndrome of facial, oral, and digital anomalies due to 7q21.2-->q22.1 duplication.

We report on an 18-year-old man with moderate mental retardation, multiple congenital anomalies and partial trisomy 7q21.2-->q22.1, as the unbalanced product of a familial balanced 7q/6q insertion translocation. To the best of our knowledge, this is the first example of interstitial trisomy 7q21.2-->q22.1 reported. The syndrome is characterized by the presence of facial, oral, and digital anomalies: 1) macrocephaly with frontal bossing, hypertelorism, small palpebral fissures with downward slant; 2) lobulated tongue, multiple intrabuccal frenula, oligodontia and enamel hypoplasia; 3) cutaneous syndactyly of fingers II-III and III-IV, broad and short fingertips with fetal pads, broad thumbs, and halluces.

Abnormalities, Multiple↗
PubMed1998

Severe mental retardation-distal arthrogryposis in the upper limbs and complex chromosomal rearrangements resulting from a 10q25-->qter deletion.

We present the first report of chromosomal rearrangement involving chromosomes 4, 10 and 12. The proband was a 42-year-old woman with severe mental retardation and multiple congenital anomalies. The most striking physical anomalies were upper limb contractures resulting in distal arthrogryposis. As upper limb flexion contractures have been previously reported in individuals with partial distal 10q deletion, this sign should be considered as part of the clinical manifestations of 10q25-->qter monosomy.

Abnormalities, Multiple↗
PubMed1998

Zygodactyly as the most striking physical anomaly in an adult male patient with pure partial trisomy 1q.

We report on a dysmorphic and mentally retarded adult male patient with partial trisomy 1q resulting from a "de novo" tandem duplication of the 1q32.3-->q42 region. The dysmorphic features consisted of facial asymmetry, synophrys, right external strabismus, teeth anomalies and bilateral syndactyly of fingers III-IV and toes II-III evoking zygodactyly. Clinical comparison is made between the present observation and previously reported cases with pure duplication including the chromosome 1 segment (q32-->q42).

Abnormalities, Multiple↗
PubMed1996

Caudal developmental field defect with female pseudohermaphroditism and VACTERL anomalies.

We describe an infant who died shortly after birth, with Potter sequence and prune belly anomaly, omphalocele, single umbilical artery, imperforate anus and micropenis with empty scrotum. Fetopathological examination revealed multiple vertebral anomalies with rudimentary sacrum, hypoplasia o2 the first metacarpus on right hand, complex cardiovascular anomalies, malrotation of intestines, a dilated and blind-ending cloaca to which both ureters and a bicornuate uterus were connected, normal ovaries, hypoplastic kidneys with cystic renal dysplasia. The descending colon ended blindly and showed a fistulous communication with the cloaca. Chromosome studies on peripheral blood lymphocytes and fibroblasts of a skin biopsy demonstrated a normal 46,XX karyotype. The possible mechanisms underlying the concurrence of a caudal developmental field defect with female pseudo-hermaphroditism and additional features of the VACTERL association are discussed.

Abnormalities, Multiple↗
PubMed1992

The role of the Y-chromosome in sex determination.

The basic plan of gonadal development in both sexes is female unless testes are induced by factor(s) of the Y chromosome, known as testis determining factor(s) (TDF). It is not clearly established whether the Y chromosome control is autonomous or under the control of a gene on the X chromosome or autosomes. A gene for the H-Y antigen (Histocompatibility-Y antigen) has been postulated to be the factor determining testicular differentiation. Recent studies have demonstrated that the gene for testis determination and the H-Y determinant are two separate entities. Although earlier cytogenetic observations localized TDF on the pericentric region of the short arm of the Y chromosome, subsequent findings by high-resolution chromosome banding and molecular analysis localise TDF to the distal part of the short arm of the Y chromosome, adjacent to the pseudoautosomal region. A candidate for TDF, the ZFY, was localised within the 140 kb interval where the position of TDF was defined, and considered as the TDF gene. However, a smaller gene sequence of 35 kb, the SRY, situated outside the 140 kb ZFY region, has recently been isolated and proved to be the only and the smallest part of the Y chromosome necessary for male sex determination.

Animals↗
PubMed1991

"Spontaneous" FRA16B is a hot spot for sister chromatid exchanges.

Six heterozygous carriers of a fragile site at 16q22 were available for the current study. We demonstrated that the observed fragile site was a "BrdUrd-sensitive" fra(16)(q22) or FRA16B, capable of spontaneous expression in some individuals (= "spontaneous" FRA16B). Significant differences either in spontaneous or in ethylmethane sulfonate (EMS)-induced sister chromatid exchange (SCE) frequencies were found between the fragile 16q22 site, whether expressed or not, and its homologous normal site. These data complement our previous findings on FRAXA and provide additional arguments indicating that fragility and SCE are variable cytogenetic expressions of the same DNA structural alteration.

Chromosome Banding↗