A new patient with Andermann syndrome: an underdiagnosed clinical genetics entity?

Andermann syndrome is an autosomal recessive disorder characterized by the agenesis of the corpus callosum and peripheral neuropathy (ACCPN). People affected by Andermann syndrome have mental retardation, areflexia and severe progressive neuropathy often accompanied by psychiatric symptoms, and they typically die in the third decade of their life. We here report the case of a 5 year-old Turkish boy born to consanguineous parents. He presented to clinical attention with delayed development and epilepsy and was found to have dysmorphic characteristics, areflexia and severe neuropathy on exam. Imaging studies were remarkable for agenesis of corpus callosum. SLC12A6 screening revealed the presence of R1011X mutation; potentially responsible for the changes in intracellular and extracellular ion concentrations, leading to defects in cortical electrical activity.

Aniridia phenotype and myopia in a turkish boy with a PAX6 gene mutation.

A boy with bilateral aniridia, iris coloboma, glaucoma, myopia and slight developmental delay was found to have a frame shift mutation in the PAX6 gene. The c.474delC mutation was de novo and both parents had a normal eye phenotype.

A boy with classical Rubinstein-Taybi syndrome but no detectable mutation in the CREBBP and EP300 genes.

Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant genetic disorder and is characterized by mental retardation, distinctive facial features, broad and often angulated thumbs and great toes. We report on a 7 year old boy with classical Rubinstein-Taybi syndrome. His facial and clinical features were very typical, including broad thumbs with radial angulation and broad great toes. Rigorous genetic analysis of the CREBBP and EP300 genes using DNA sequencing and multiple ligation-dependent probe amplification (MLPA) revealed no causative mutation in this boy, only a hitherto unreported but paternally inherited heterozygous sequence alteration, c.506 1+9C>T in IVS 30-31, which most likely represents a normal variant (NetGene 2 splice prediction software). We question if this boy could have a hitherto undetectable mutation type.

A unique case of a patient with partial trisomy 22 and lipodystrophy: is it a new syndrome due to an IGF-IR mutation?

A newborn male presented with intestinal malrotation, facial anomalies, hypertrichosis, hypertrophic, hyperpigmented nipples and enlarged genitals with a hyperpigmented scrotum. In addition, the patient displayed a marked lipodystrophy of trunk and limbs. His karyotype demonstrated a small supernumerary NOR-positive marker chromosome that was subsequently identified as del(22)(q12->qter). This extra structurally abnormal chromosome probably derives from a maternal balanced translocation, which was found by karyotype analysis of the mother. The patient's growth hormone (GH) serum levels were elevated, whereas serum insulin-like growth factor 1 (IGF-I) was almost undetectable. Molecular genetic analysis of the IGF-I and type 1 IGF receptor (IGF-IR) genes revealed a heterozygous mutation within exon 21 of the IGF-IR (Pro1257Ser). Findings in our patient correlate to a large extent with partial trisomy 22. Phenotypic variation from classical partial trisomy 22 syndrome may lie within the variability of this syndrome, originate from disturbances within the GH-IGF/IGF-IR axis or, alternatively, reflect the pathogenesis of a new syndrome due to the synergistical impact of the combination of the genetic aberrations. Additional studies are necessary to confirm or refute this hypothesis.

Autism with del15p.11.1: case report with a new cytogenetic finding.

Autism with dell5Sp.11.1: case report with a new cytogenetic finding: Autism is a neurodevelopmental disorder and believed to be mainly genetic in origin, and environmental factors may modulate phenotypic expression. Less than four percent of cases of autism are associated with chromosomal abnormalities. Cytogenetic abnormalities found at the 15q11-q13 locus are reported most frequently in patients with autism. We performed GTG-banding and FISH studies to the present case and his parents and found a maternally inherited deletion on chromosome 15p in this case. With an understanding of the many genetic causes of autism, prenatal screening and counseling may one day become available for affected families as more autism-causing conditions become diagnosable.

A case with a rare chromosomal abnormality: isochromosome 18p.

Isochromosome 18p (i(18p)), is a rare chromosomal disorder that occurs once in about every 140,000 live births and affects males and females equally. Most of the cases are due to a de novo formation but in the literature familial cases were reported. Here, we report a young female with dysmorphic features as microcephaly, frontal bossing, strabismus, low-set ears, small pinched up nose, small mouth, high palate and long philtrum, presenting a small metacentric chromosome. Besides the dysmorphic features she also has gastroesophageal reflux, spasticity, strabismus and specific brain MRI findings as dilatation of the right lateral ventricle trigonum occipital horn (colpocephaly), thinning of the corpus callosum especially of the posterior part and abnormality of the white matter myelinisation at the frontal and occipital region. Particularly the MR findings are rarely reported in the literature.

Mixed gonadal dysgenesis with 45,X/46,X,idic(Y)/46,XY,idic(Y) karyotype.

To present the new karyotype with mixed gonadal dysgenesis, the aetiologic approach and difficulties in genetic counseling in mosaic sex chromosome disorders. We report a fourteen-year-old boy presented with slightly ambigious genitalia. Cytogenetic and fluorescence in situ hybridization investigations were carried out on his peripheral lymphocytes. As a result, three cell lines, 45,X, 46,X,idic(Y)(q11.2) and 46, XY were observed. A markedly higher percentage of Y-containing cells was observed in the blood (68%), which was not considered to be the major reason why the case did not have distinct ambiguous genitalia. We suggest that study of cytogenetic and molecular mosaicism involving sex chromosomes may help to further unravel the mysterious process in mixed gonadal dysgeneic patients.

Lack of association between the Glu298Asp polymorphism of endothelial nitric oxide synthase and slow coronary flow in the Turkish population.

BACKGROUND: Coronary endothelial dysfunction plays an important pathogenetic role in patients with slow coronary flow (SCF). No data exist regarding the possible contribution of the Glu298Asp polymorphism genotype of the endothelial nitric oxide synthase (eNOS) gene to human SCF in the literature. OBJECTIVE: To investigate the association between SCF and the Glu298Asp polymorphism of the eNOS gene. METHODS: The study population consisted of 85 consecutive patients. The patient group included 66 patients with angiographically proven normal coronary arteries with SCF, and 19 subjects with normal coronary arteries with no SCF. The thrombolysis in myocardial infarction frame count was used for the diagnosis of SCF. The Glu298Asp polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The baseline characteristics were similar between the two groups, except for high-density lipoprotein cholesterol, which was higher in the SCF group than in the controls. The genotype distribution of Glu298Asp was as follows: GG 26%, GT 56% and TT 12%, where G is guanine and T is thymine. There was no difference in the frequency of the various genotypes or the alleles in patients with SCF versus normal controls. CONCLUSIONS: The Glu298Asp polymorphism genotype of the eNOS gene is not a risk factor for SCF in the present study population.

Fluorescence in situ hybridization and single nucleotide polymorphism of a new case with inv dup del(8p).

Fluorescence In Situ Hybridization and single nucleotide polymorphism of a new case with inv dup del(8p): Inverted duplication deletion of 8p [inv dup del(8p)] is a complex chromosome rearrangement leading among others to deletion of the chromosome region distal to the duplication in 8p. A new case with an inverted duplication deletion of 8p and the results of SNP-array analysis and fluorescence in situ hybridization (FISH) are reported here. Our results are in concordance with earlier reported inv dup del(8p) cases.

A provisionally unique syndrome with features including "molar tooth" sign and "femoral hypoplasia".

A provisionally unique syndrome with features including "molar tooth" sign and "femoral hypoplasia": The femoral-facial syndrome (FH-UFS) is a rare syndrome of uncertain inheritance comprising hypoplastic femora, microretrognathia, and peculiar facies. We describe a new case with facial dysmorphism, broad chest and widely spaced nipples, shorter right lower limb with femoral hypoplasia and unilateral fibular hemimelia, bilateral absence of 5th metatarsal and toe, and bilateral talipes equinovarus. In addition, a complete agenesis of corpus callosum, cerebellar vermis hypoplasia with molar tooth sign and Dandy-Walker malformation were present. Posterior fossa abnormalities in FH-UFS have not been described in the literature until now, thus extending the clinical spectrum of this entity. Other syndromes characterized by femoral hypoplasia and/or molar tooth sign are also discussed.

Can the classical euchromatic variants of 9q12/qh+ cause recurrent abortions?

Various heteromorphisms of the 9q heterochromatic area have been reported, and the 9q12/qh variant has been postulated to be more prevalent than initially perceived. Of note is that all probands are clinically normal. This paper documents two cases with a G-band within the 9q12h region and recurrent miscarriages. Patient 1 is a 22-year-old woman with a history of 2 miscarriages. Patient 2 is a 19-year-old woman with a history of 3 miscarriages. Chromosome analysis of the patients showed 46,XX,9q12h+. Thus, the existence of a G+ band in 9qh may not be a normal variant in humans. We suggest IVF and preimplantation genetic diagnosis in such patients.

Scoliosis, blindness and arachnodactyly in a large Turkish family: is it a new syndrome?

In this report we have described an affected sib in a large Turkish family who appears to have a new distinct dominantly-inherited blindness, scoliosis and arachnodactyly syndrome. The combination of clinical abnormalities in these patients did not initially suggest Marfan syndrome or other connective tissue disorders associated with ectopia lentis. The proband was a 16-year-old boy who was referred to our clinics for scoliosis. He had arachnodactyly of both fingers and toes. He had been suffering from progressive visual loss and strabismus since he was eight-years-old. His 20-year-old brother had severe kyphoscoliosis, and arachnodactyly of fingers and toes. He was 130 cm tall and was bilaterally blind. His 23-year-old sister had only eye findings but no arachnodactyly or scoliosis. His 60-year-old father had mild scoliosis, blindness and arachnodactyly and mother was normal. We performed routine mutation analyses in the genes FBN1, TGFBR1 and TGFBR2, but no mutation has been detected. Our Turkish patients are most likely affected by a hitherto unrecorded condition which is caused by an autosomal dominant gene defect with variable expression but we can not exclude multigenic inheritance. Further studies are needed to assess the contribution of sex influence to the syndrome because the female relative is less affected.