Purchase individual online access for 1 year to this journal.
Price: EUR N/A
Journal of Pediatric Genetics is an English multidisciplinary peer-reviewed international journal publishing articles on all aspects of genetics in childhood and of the genetics of experimental models. These topics include clinical genetics, molecular genetics, biochemical genetics, formal genetics, neuropsychiatric genetics, behavioral genetics, community genetics, cytogenetics, hereditary or syndromic cancer genetics, genetic mapping, reproductive genetics, fetal pathology and prenatal diagnosis, multiple congenital anomaly syndromes, and molecular embryology of birth defects.
Journal of Pediatric Genetics provides an in-depth update on new subjects, and current comprehensive coverage of the latest techniques in the diagnosis of childhood genetics.
Journal of Pediatric Genetics encourages submissions from all authors throughout the world.
The following articles will be considered for publication: editorials, original and review articles, short report, rapid communications, case reports, letters to the editor, and book reviews. The aim of the journal is to share and disseminate knowledge between all disciplines that work in the field of pediatric genetics.
Abstract: The insulin-like growth factor 1 receptor (IGF1R) is a key factor in intrauterine and postnatal growth by mediating the biological function of IGF-I. Mutations of IGF1R gene are usually associated with growth retardation, but the clinical picture of IGF1R mutation carriers is heterogeneous. Indeed, these patients show clinical signs compatible with Silver-Russell syndrome (SRS), and some IGF1R mutation carriers have been identified in SRS cohorts. We therefore investigated deoxyribonucleic acid samples of 19 growth-retarded patients with SRS features. Apart from 8 non-pathogenic variants, we detected heterozygosity for the unknown duplication, c.1056_1057dup, leading to a premature termination in one patient…and his growth retarded sister. Due to its nature, we assumed that this variant is probably pathogenic. However, the patient and his sister exhibited spontaneous catch-up growth in later life. We therefore hypothesize that the c.1056_1057dup does not result in a significant disruption to the GH-IGFI axis. Thus, this IGF1R mutation without obvious clinical consequence might challenge the actual concept of IGF1R haploinsufficiency as a general cause for disturbed growth in IGF1R mutation carriers. In the future, mutation analysis of IGF1R should be considered in growth-retarded patients with microcephaly and minor SRS features, but not in probands with the characteristic SRS phenotype including macrocephaly.
Abstract: Insulin-like growth factor 2 receptor (IGF2R ) and insulin-like growth factor 2 (IGF2 ) genetic variants have been inconsistently associated with low birth weight and birth length in Caucasian and Asian infants, however few studies have included African Americans (AA). Generalized linear models and logistic regression models were used to examine associations between IGF2R single nucleotide polymorphisms (SNP) rs629849 and rs8191754, and IGF2 SNP rs680 and infant anthropometric measurements, in a racially diverse birth cohort in Durham County, North Carolina. Caucasian American (CA) carriers of the IGF2R SNP rs629849 were heavier (P = 0.02) and longer…(P = 0.003) at birth, however body size at age 1 yr was similar to that of AA. Birth length significantly differed between carriers and non-carriers of the IGF2 rs680 variant in both AA (P = 0.04) and CA infants (P = 0.03). Both AA and CA carriers were 1 cm shorter at birth compared to non-carriers. We found no evidence for an association between rs8191754 and infant anthropometric measurements. Associations between SNPs and one year weight gain were only observed for rs680; CA infant carriers of rs680 variants weighed less than non-carriers at year one (P = 0.03); however, no associations were found in AA infants at year one. Larger studies using ancestral markers are required to disentangle these associations.
Abstract: Classic nephropathic cystinosis (CNC) is an autosomal recessive and infrequent inborn metabolic disease that should be suspected in all children who show failure to thrive and renal Fanconi syndrome (RFS). Slit-lamp examination reveals pathognomonic corneal deposits of cystine crystals in virtually all affected individuals after 12–16 mo of age. A diagnosis of CNC is difficult to confirm in children living in Mexico and most Latin American countries, because cystine levels can be measured only at a few locations. We report the cystinosin genotype findings in 15 Latin American patients with a high clinical suspicion of CNC mainly due to RFS…(n =13), although five of them lacked proper ophthalmologic assessment, despite being more than 1-year-old. Molecular analysis confirmed diagnosis of CNC in six (40%) of the 15 patients, five of them with RFS and cystine crystals. The remaining nine (60%) patients had a normal genotype. The predominance of a normal cystinosin genotype in eight of 13 patients with RFS (61.50%) reinforces the need to perform slit-lamp examinations in all patients with RFS over 1 yr of age, prior to measuring cystine or performing molecular cystinosin study, both methods not readily available throughout Latin America.
Abstract: Dent’s disease is an X-linked proximal tubulopathy characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis and progressive renal failure. This disorder is frequently caused by mutations in the CLCN5 gene encoding the electrogenic chloride/proton exchanger ClC-5. Occasionally, Dent’s disease has been associated to atypical cases of asymptomatic proteinuria with focal glomerulosclerosis. Twelve unrelated patients with Dent’s disease, including two who presented with asymptomatic proteinuria and developed glomerulosclerosis, were studied. Mutational analysis of the CLCN5 gene was performed by DNA sequencing. We identified thirteen distinct CLCN5 mutations in the twelve patients. Seven of these mutations, p.P416fsX* 17, p.[H107P, V108fs*…27], p.G466D, p.G65R, p.G462S, p.Y164* and c.723+1G >T, were novel and possibly pathogenic. In one family, the patient’s mother was not a carrier of the respective mutation. Our results increased the spectrum of CLCN5 disease causing defects with seven new pathogenic mutations and established a de novo origin in one of them. Remarkably, three new missense mutations, p.G466D, p.G65R and p.G462S, affect highly conserved glycine residues located in transmembrane α-helix GxxxG packing motifs. The two atypical cases further support that the diagnosis of Dent’s disease should be considered in children with asymptomatic proteinuria and focal glomerulosclerosis and without evidence of primary glomerular disease.
Abstract: Monosomy 18p syndrome is a rare chromosomal disorder with varying phenotypic and clinical manifestations. Dysmorphism, growth delay, delayed speech and mental retardation are a few of the commonest features observed. The cytogenetic findings also vary and may comprise a pure deletion of the entire 18p arm or a deletion of a part of the 18p arm, if involved in a translocation with other chromosomes. Monosomy 18p may either occur by itself or with a structural alteration of the remaining chromosome 18, as a ring or as an isochromosome. The clinical presentation of this syndrome often overlaps with other syndromes. Establishing…a cytogenetic diagnosis and understanding the location of the breakpoints is crucial for precise management and follow-up. We present here a rare case with mosaicism for a de novo deletion of 18p with isochromosome 18q in a boy born to a consanguineous Omani couple.
Abstract: We report on the cytogenetic and molecular investigations of constitutional de-novo ring chromosome 13s in three unrelated patients for better understanding and delineation of the phenotypic variability characterizing this genomic rearrangement. The patient’s karyotypes were as follows: 46,XY,r(13)(p11q34) dn for patients 1 and 2 and 46,XY,r(13)(p11q14) dn for patient 3, as a result of the deletion in the telomeric regions of chromosome 13. The patients were, therefore, monosomic for the segment 13q34 → 13qter; in addition, for patient 3, the deletion was larger, encompassing the segment 13q14 → 13qter. Fluorescence in situ hybridization confirmed these rearrangement and array CGH technique…showed the loss of at least 2.9 Mb on the short arm and 4.7 Mb on the long arm of the chromosome 13 in patient 2. Ring chromosome 13 (r(13)) is associated with several phenotypic features like intellectual disability, marked short stature, brain and heart defects, microcephaly and genital malformations in males, including undescended testes and hypospadias. However, the hearing loss and speech delay that were found in our three patients have rarely been reported with ring chromosome 13. Although little is known about its etiology, there is interesting evidence for a genetic cause for the ring chromosome 13. We thus performed a genotype-phenotype correlation analysis to ascertain the contribution of ring chromosome 13 to the clinical features of our three cases.
Keywords: Array-CGH, FISH, intellectual disability, ring chromosome 13
Abstract: We report a 32-month-old female of Peruvian ethnicity identified with a rare 20q13.2-q13.33 deletion using microarray analysis. She presented with intellectual disability, absent speech, hypotonia, pre- and post-natal growth retardation and an abnormal face with a unilateral cleft lip. Clinical features and genetic findings with the loss of 30 genes, including GNAS , MC3R , CDH4 and TFAP2C , are described in relationship to the very few cases of 20q13 deletion reported in the literature. Deletion of this region may play an important role in neurodevelopment and function and in causing specific craniofacial features.
Abstract: 5p deletion syndrome or Cri du Chat syndrome is a autosomal deletion syndrome, caused by the de novo deletion of chromosome 5p in the majority of the cases. Clinical features include developmental delay, microcephaly, subtle facial dysmorphism and high-pitched cry. With the advent of newer techniques such as multiplex ligation-dependent probe amplification, rapid diagnosis is possible and chromosomal microarray helps in accurate delineation of the breakpoints. In this study, we characterized probands from two Indian families who had duplication of another chromosome in addition to deletion of 5p region. In the first family, two females of 3 and 5 yr…of age had deletion of 5p15.33p15.2 (14.7 Mb) and duplication of 8q24.21q24.3 (15.4 Mb). Proband in the second family was a 2-year-old female and had deletion of 5p15.33p14.3 (22.55 Mb) along with duplication of 12p13.33p13.31 (7.7 Mb). In both the families, father was balanced translocation carrier of the chromosomes involved. Patients in family 1 had overwhelming features of 5p deletion while patient in family 2, besides having features of 5p deletion, showed many features of 12p duplications. Prenatal diagnosis was possible in both the families. To the best of our knowledge, this is the first detailed molecular cytogenetic analysis and prenatal diagnosis report of 5p deletion syndrome from India.