Study on clinical features and diagnostic methods of prenatal Wolf-Hirschhorn syndrome / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical features of fetuses with Wolf-Hirschhorn syndrome(WHS) and explore the diagnostic methods and prenatal ultrasound characteristics and provide evidence for prenatal genetic counseling.@*METHODS@#We retrospectively analyzed 5 cases of WHS fetuses diagnosed from March 2016 to February 2020, and analyzed the results of chromosomal karyotype analysis and chromosomal microarray analysis (CMA) of the fetuses.@*RESULTS@#Five cases of WHS were detected by CMA, four cases were detected by karyotype analysis. Prenatal ultrasound revealed 4 abnormalities, of which 3 had intrauterine growth restriction, and only 1 had abnormalities of the maxillofacial region. The sequence of the fragments was 4p16.3p16.1 with a loss of 6.5 Mb, 4p16.3p15.32 with a loss of 15.6 Mb combined with 2p25.3 increased by 906kb, 4p16.3p15.31 with a loss of 20.4 Mb, 4p16.p15.1 with a loss of 35 Mb and 4p16.3p14 with a loss of 37 Mb.@*CONCLUSION@#Fetal growth restriction may be one of the early manifestations of WHS. Absence of fetal facial abnormality by prenatal ultrasound screening cannot exclude WHS. Karyotype analysis may miss the diagnosis of WHS, while combined CMA techniques can improve the diagnostic accuracy.

Prenatal diagnosis for a pedigree affected with Wolf-Hirschhorn syndrome due to a subtle chromosomal translocation / 中华医学遗传学杂志

OBJECTIVE@#To make molecular diagnosis of an infant affected with severe developmental delay and multiple birth defects, assisting prenatal diagnosis for the second pregnancy.@*METHODS@#Standard G-banded karyotyping was performed for the fetus and his parents. Single nucleotide polymorphism array (SNP array) was used to detect submicroscopic chromosomal aberration. Fluorescence in situ hybridization (FISH) was employed to determine the parental origin of the aberration.@*RESULTS@#Both the proband and the fetus harbored a 5.4 Mb distal 4p deletion and a 6.9 Mb distal 6q duplication. FISH confirmed that the mother has carried a balanced translocation involving 4p and 6q.@*CONCLUSION@#The unbalanced chromosomal aberration in the proband and the fetus were both derived from the mother. Both patients showed a Wolf-Hirschhorn syndrom phenotype and partial phenotype of 6q trisomy. SNP array combined with FISH are essential for the detection of cryptic chromosomal aberrations which may be missed by coventional karyotyping analysis.

Phenotypic and genetic analysis of a pedigree with 4p16 microduplication and 8p23 microdeletion / 中华医学遗传学杂志

OBJECTIVE@#To explore the nature and origin of chromosomal copy number variants (CNVs) in a pedigree affected with mental retardation.@*METHODS@#Genomic CNVs of the proband were analyzed by next generation sequencing (NGS). Chromosomal karyotypes of the proband and his relatives were analyzed with high-resolution karyotyping and fluorescence in situ hybridization (FISH).@*RESULTS@#Clinical phenotypes of the proband and other patients from the pedigree included mental retardation and mild dysmorphism. The results of NGS revealed that the proband carried a 16.24 Mb microduplication at 4p16.3-15.32 and a 2.2 Mb microdeletion at 8p23.3-23.2. Other patients of the pedigree harbored the same variants, while those without the phenotypes did not harbor the variants. The results of high-resolution karyotyping and FISH revealed that the mother of the proband carried a reciprocal translocation between 4p and 8p, and her karyotype was 46,XX,t(4;8)(p16;p23). No karyotypic abnormality was detected in his father.@*CONCLUSION@#The abnormal phenotypes of this pedigree may be attributed to 4p microduplication in conjunct with 8p microdeletion derived from a maternal balanced translocation between 4p and 8p.

Variação de número de cópias no cromossomo 4: uma possível síndrome genética? / Number copies variation in chromosome 4: a possible genetic syndrome?

INTRODUÇÃO: Variantes de número de cópias (CNVs) são variações no número de cópias de uma região da sequência genômica, descrevendo deleções ou ganhos em relação a indivíduos controle. Podem ser comuns e de caráter benigno, de significado incerto ou variantes patogênicas. Para interpretação, classificação e avaliação de significado clínico, é realizado comparação dos resultados nas bases de dados do laboratório e análise da literatura científica. OBJETIVO: Relatar caso de adolescente com duplicação/triplicação no cromossomo 4 com déficit cognitivo e dismorfismo facial e discutir se essa CNV pode ser responsável pelos achados clínicos. RELATO DE CASO: Paciente de 15 anos, sexo feminino, levada ao ambulatório de Genética para investigação de possível síndrome genética. Pais consanguíneos (primos). Desde a infância apresenta estrabismo divergente, atraso no desenvolvimento neuropsicomotor com dificuldade de fala. Cursou com síndrome hipotônica com espasmos mioclônicos. Evoluiu com déficit cognitivo. A Ressonância magnética de encéfalo demonstrou comprometimento de hemisférios cerebelares e atrofia de ponte e mesencéfalo. Cariótipo normal (46, XX) e hibridização genômica comparativa baseada em microarranjos (a-CGH) revelou duplicação/ triplicação na região 4p 15.32p15.31, variante de significado incerto. CONCLUSÃO: Destaca-se a importância da investigação através de análises cromossômicas por microarranjos em pacientes com deficiência intelectual, síndrome do espectro do autismo e múltiplas malformações congênitas - isto para aprimoramento diagnóstico, cuidados médicos específicos e aconselhamento genético.

INTRODUCTION: Copy number variants (CNVs) are variations in the number of copies of a region of the genomic sequence, describing deletions or gains in relation to control individuals. They may be common and of benign nature, of uncertain meaning or pathogenic variants. For interpretation, classification and evaluation of clinical significance, a comparison of the results in the laboratory databases and analysis of the scientific literature is performed. OBJECTIVE: To report a case of adolescent with duplication / triplication on chromosome 4 with cognitive deficit and facial dysmorphism and to discuss whether this CNV can be responsible for the clinical findings. CASE REPORT: A 15-year-old female patient was taken to the Genetics outpatient clinic to investigate a possible genetic syndrome. Consanguineous parents. Since childhood, she has divergent strabismus, delayed neuropsychomotor development with speech difficulties. She developed with hypotonic syndrome with myoclonic spasms. She evolved with cognitive deficit. Magnetic resonance imaging of brain showed compromised cerebellar hemispheres and atrophy of the bridge and midbrain. Normal karyotype (46, XX) and comparative genomic hybridization based on microarrays (a-CGH) revealed duplication / triplication in the region 4p 15.32p15.31, variant of uncertain meaning. CONCLUSION: The importance of research through chromosomal analysis by microarray in patients with intellectual disability, autism spectrum syndrome and multiple congenital malformations is highlighted ­ this for diagnosis improvement, specific medical care and genetic counseling.

Pain insensitivity in a child with a de novo interstitial deletion of the long arm of the chromosome 4: Case report / Insensibilidad al dolor en un niño con una deleción intersticial de novo del brazo largo del cromosoma 4

Terminal and interstitial deletions of the distal segment of the long arm of chromosome 4 (Cr4q del) are not common genetic disorders. The severity of the phenotype is correlated with the size of the deletion because small deletions have little clinical impact, whereas large deletions are usually associated with multiple congenital anomalies, postnatal growth failure, and moderate to severe intellectual disability. Alteration in pain tolerance has not been included among these features, also in case of large deletions. The purpose of this report is to document a case of a child affected by interstitial Cr4q del, expressing pain insensitivity as clinical feature not previously described. We also offer a discussion on genetic disorders featuring pain insensitivity/indifference. Case report. A Caucasian girl aged 12 came to our observation for a developmental delay with multiple congenital abnormalities and moderate intellectual disability (IQ 47). A de novo interstitial Cr4 del between band q31.3 and q32.2 (Cr4 del q31.3 to q32.2) was found. The child also expresses no evidence of pain perception to injures which normally evoke pain. Consequently, she is affected by severe disability caused by painless injuries and self-injurious behaviours, such as excessive self-rubbing and scratching. The neurological examination manifested high pain threshold with preserved tactile sensitivity. Conclusions. This is the first report of pain insensitivity in a patient with a specific genetic deletion involving the interstitial region of the distal long arm of Cr4. Moreover, this report could serve as a useful model to better understand mechanisms of pain perception and its modulation.

Prenatal diagnosis of a case with 46,XX,del(4),dup(21) / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genetic cause and prognosis of a fetus with a rare karyotype.</p><p><b>METHODS</b>Fluorescence in situ hybridization (FISH) was used for verifying a structural chromosomal abnormality detected by conventional karyotyping analysis. Whole genome DNA microarray was used to analyze copy number variations carried by the fetus.</p><p><b>RESULTS</b>The fetus was found to have a 46,XX,dup(21)(?q21q22) karyotype, which was verified by FISH analysis as repetition of chromosome 21 region, namely nuc ish 21q22×3. Whole genome DNA microarray confirmed that there was a 17.87 Mb duplication in the 21q21.3q22.3 region, which involved GATA1, JAK2 and ALL genes and spanned the Down syndrome region. The genes are implicated in craniofacial abnormalities, cardiac abnormalities, mental retardation, growth retardation, limb abnormalities. In addition, there was also an 8.43 Mb deletion in the 4p16.1p16.3 region, which involved FGFR3, LETM1, WHSC1 and WHSC2 and other 64 OMIM genes and spanned the Wolf-Hirschhorn syndrome region. The genes are implicated in growth retardation, craniofacial abnormalities, cardiac abnormalities, mental retardation, and hypotonia. After consultation, the family chose to terminate the pregnancy at 25th week of gestation.</p><p><b>CONCLUSION</b>FISH can help to verify structural chromosome abnormalities suspected by conventional karyotyping analysis. Combined with whole genome microarray, these can determine copy number variation and its region containing the disease genes, and facilitate clinical analysis of the fetus.</p>

Prenatal diagnosis of 4p deletion syndrome: A case series report

The 4p deletion syndrome, also known as Wolf-Hirschhorn syndrome, is a well-known genetic disorder caused by a partial deletion of the short arm of chromosome 4. The great variability in the extent of the 4p deletion and the possible contribution of additional genetic rearrangements leads to a wide spectrum of clinical manifestations. Herein, we present our experience with eight cases of 4p deletion syndrome, ascertained prenatally between 1998 and 2016 at our hospital.

Abnormalities in Chromosomes 1q and 13 Independently Correlate With Factors of Poor Prognosis in Multiple Myeloma

BACKGROUND: We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. METHODS: The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. RESULTS: MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. CONCLUSIONS: This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis.

A Rare Case of Pediatric T Lymphoblastic Leukemia With t(11;17)(q23;q21) Involving Mixed-Lineage Leukemia Gene Rearrangement

No abstract available.

Efficiency to Discovery Transgenic Loci in GM Rice Using Next Generation Sequencing Whole Genome Re-sequencing

Molecular characterization technology in genetically modified organisms, in addition to how transgenic biotechnologies are developed now require full transparency to assess the risk to living modified and non-modified organisms. Next generation sequencing (NGS) methodology is suggested as an effective means in genome characterization and detection of transgenic insertion locations. In the present study, we applied NGS to insert transgenic loci, specifically the epidermal growth factor (EGF) in genetically modified rice cells. A total of 29.3 Gb (~72x coverage) was sequenced with a 2 x 150 bp paired end method by Illumina HiSeq2500, which was consecutively mapped to the rice genome and T-vector sequence. The compatible pairs of reads were successfully mapped to 10 loci on the rice chromosome and vector sequences were validated to the insertion location by polymerase chain reaction (PCR) amplification. The EGF transgenic site was confirmed only on chromosome 4 by PCR. Results of this study demonstrated the success of NGS data to characterize the rice genome. Bioinformatics analyses must be developed in association with NGS data to identify highly accurate transgenic sites.

Prenatal diagnosis of a case with combined Wolf-Hirschhorn syndrome and Jacobsen syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect chromosomal imbalance in a fetus with complex congenital heart disease, and to correlate the genotype with the phenotype.</p><p><b>METHODS</b>Routine G-banding was carried out to analyze the karyotypes of the fetus and its parents, and single nucleotide polymorphisms array (SNP-array) was used for delineating fine genomic aberrations. The detected aberrations were confirmed with multiplex ligation-dependent probe amplification (MLPA).</p><p><b>RESULTS</b>The fetus and its parents all showed a normal karyotype, while array-SNP has detected a 13.87 Mb duplication at 4p16.3-p15.33 and a 15.65 Mb deletion at 11q23.3-q25 in the fetus. The results were confirmed by the MLPA assay.</p><p><b>CONCLUSION</b>The partial trisomy 4p (Wolf-Hirschhorn syndrome) and partial monosomy 11q (Jacobsen syndrome) probably underlie the complex heart defects detected in the fetus. Analysis of the karyotypes of its parents offered no help for the determination of the aberrant type and recurrent risk. Compared with routine karyotype analysis, aberrant regions can be identified with array-SNP with greater resolution and accuracy. This has provided useful information for prenatal diagnosis and genetic counseling.</p>

Analysis of genomic copy number variations in two sisters with primary amenorrhea and hyperandrogenism / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze genomic copy number variations (CNVs) in two sisters with primary amenorrhea and hyperandrogenism.</p><p><b>METHODS</b>G-banding was performed for karyotype analysis. The whole genome of the two sisters were scanned and analyzed by array-based comparative genomic hybridization (array-CGH). The results were confirmed with real-time quantitative PCR (RT-qPCR).</p><p><b>RESULTS</b>No abnormality was found by conventional G-banded chromosome analysis. Array-CGH has identified 11 identical CNVs from the sisters which, however, overlapped with CNVs reported by the Database of Genomic Variants (http://projects.tcag.ca/variation/). Therefore, they are likely to be benign. In addition, a -8.44 Mb 9p11.1-p13.1 duplication (38,561,587-47,002,387 bp, hg18) and a -80.9 kb 4q13.2 deletion (70,183,990-70,264,889 bp, hg18) were also detected in the elder and younger sister, respectively. The relationship between such CNVs and primary amenorrhea and hyperandrogenism was however uncertain. RT-qPCR results were in accordance with array-CGH.</p><p><b>CONCLUSION</b>Two CNVs were detected in two sisters by array-CGH, for which further studies are needed to clarify their correlation with primary amenorrhea and hyperandrogenism.</p>

A Case of Wolf-Hirschhorn Syndrome with Periventricular Nodular Heterotopia Presenting with Status Epilepticus

Wolf-Hirschhorn syndrome is a congenital disorder associated with partial deletion of the short arm of chromosome 4. The majority of patients showed characteristic facial anomalies - so called "Greek-Helmet" appearances - mental retardation, growth retardation, and developmental delay. Here we report the case of a 3-year-old girl who was diagnosed as having Wolf-Hirschhorn syndrome immediately at birth with distinct facial anomalies and an abnormal chromosomal karyotype [46,XX,del(4)(p14)]. The patient later presented with status epilepticus and magnetic resonance imaging showed periventricular nodular heterotopia.

Clinical and Molecular Delineation of a Novel De Novo 4q28.3-31.21 Interstitial Deletion in a Patient with Developmental Delay

No abstract available.

Array comparative genomic hybridization detection of a de novo 4q21.21-q22.1 deletion in a child with severe growth retardation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a child with developmental delay, severe mental retardation, speech delay and muscular hypotonia.</p><p><b>METHODS</b>The karotypes of the child and her parents were analyzed with G-banding analysis. Their genome DNA was also analyzed with array comparative genomic hybridization (array-CGH).</p><p><b>RESULTS</b>No karyotypic abnormality was detected at cytogenetic level. However, array-CGH has identified a de novo 4q21.21-q22.1 deletion in the child, which has a size of 12.1 Mb.</p><p><b>CONCLUSION</b>The de novo interstitial 4q21.21-q22.1 deletion probably underlies the main clinical manifestation in the child. Array-CGH is useful for diagnosing children with multiple congenital anomalies with unclear etiology.</p>

Detecting the abnormal expression of PDGFRA gene in eosinophilia by FISH / 中国实验血液学杂志

This study was aimed to investigate the abnormal expression of PDGFRA gene in eosinophilia by FISH. Translocations of PDGFRA gene in 13 patients with eosinophilia were detected by using 4q12 three-color probe and FISH technology. Fifteen people were used as control to establish the normal cut-off value of fluorescence signal of PDGFRA. The results indicated that 1 out of 13 patients with eosinophilia was corrected and was diagnosed as CML. The fusion gene of FIP1L1-PDGFRA (F/P) was found in 2 patients and the positive rate of F/P fusion gene detected by probe 4q12 was 17% in the 12 patients with eosinophilia. Other translocation forms involving PDGFRA gene were not found. It is concluded that a variety of translocation forms of PDGFRA gene can be detected in patients with eosinophilia by using 4q12 three-color probe and FISH technology, which can provide important information for assessing diagnosis and treatment.

Caracterización citogenética y molecular de una paciente ecuatoriana con cromosoma 4 en anillo: análisis clínico comparativo con 37 casos internacionales / Cytogenetic and molecular characterization of a Ecuadorian patient with ring chromosome 4: comparative clinical analysis with 37 international cases

Los cromosomas en anillo son alteraciones genéticas muy inusuales, consecuencia de deleciones en las regiones terminales y de la unión de los extremos expuestos del cromosoma afectado. En un cromosoma 4 en anillo las regiones que con más frecuencia se afectan son 4p16.3 del brazo corto y 4q35.2 del brazo largo. Sujeto y métodos Se presenta el caso de una paciente con cromosoma 4 en anillo diagnosticado cuando tenía diez días de edad. Al examen clínico presentó dismorfogénesis importante: frente plana, nariz puntiforme, implantación baja de pabellones auriculares, clinodactilia del quinto dedo, microcefalia, micrognatia, un orifcio en la región lumbosacra, estatura baja y retardo mental leve. A los 10 años de edad se le realizó una evaluación citogenética con técnicas más modernas: hibridación in situ fluorescente (FISH) y mapeo genético por arrays de ADN. El fenotipo de la paciente fue comparado con 37 casos reportados en la literatura internacional. Resultados En el análisis clínico de la paciente y los 37 casos internacionales se encontró alrededor de 41 características clínicas diferentes y variables en cada sujeto. Las más frecuentes fueron retraso en el crecimiento (78%), microcefalia (67%), retardo mental (62%), bajo peso al nacer (48%), clinodactilia del quinto dedo (37%), micrognatia (29%), hipertelorismo (21%) y alguna cardiopatía (18%). El estudio citogenético de la paciente a los diez días de edad mostró un cariotipo en mosaico 46,XX/46,XX,r(4) con anillo del cromosoma 4 en el 80% de las metafases. A los diez años de edad se encontró r(4) en el 90% de las células. El análisis por FISH reveló un cariotipo 46,XX,r(4).ish r(4)(p16.3q35.2) (492870-793359-,190183811-190408149-). Los arrays evidenciaron las regiones de pérdida de los brazos cortos y largos del cromosoma 4 involucrados en la formación del anillo. Los genes que con seguridad inciden en el fenotipo de la paciente en estudio son LETM1, WHSC1, WHSC2, MIR943, TACC3, IDUA, C4orf48 para retardo mental; LETM1 y WHSC1 para microcefalia y KIAA1530 para retraso en el crecimiento.

Ring chromosomes are rare chromosomal structure abnormalities; they are formed when a chromosomal deletion leads to the fusion of both ends of the chromosome. The most frequent altered regions in ring chromosome 4 are 4p16.3 in short arm and 4q35.2 in long arm. Subject and methods Here we report a 10 days old female patient whose frst cytogenetic diagnosis showed a ring chromosome 4. Clinical examination showed congenital abnormalities including flattened forehead, prominent nose, low set ears, clinodactyly of the ffth fnger, microcephaly, micrognathia, small sacrococcygeal dimple, short stature and mild mental retardation. At the aged of ten fluorescence in situ hybridization (FISH) and DNA microarrays were performed. Finally, patient phenotype was compared with other 37 cases reported in the literature. Results The clinical analysis between the patient and the 37 cases reported showed about 41 different clinical features that vary between each individual. The most frequent features were growth retardation (78%), microcephaly (67%), mental retardation (62%), short stature at birth (48%), clinodactyly of the ffth fnger (37%), micrognathia (29%), hypertelorism (21%) and some type of cardiopathy (18%). Chromosome analysis of the patient at 10 days old appeared as a chromosomal mosaicism 46,XX/46,XX,r(4), with ring chromosome 4 in 80% of the metaphases analyzed. At 10 years old of the patient it was observed r(4) in 90% of the cells. FISH analysis showed a karyotype 46,XX,r(4).ish r(4)(p16.3q35.2) (492870-793359-,190183811-190408149-). The arrays showed deleted regions at the short and long arms of chromosome 4 involved in the formation of ring chromosome. The genes that are manifested in the patient phenotype are LETM1, WHSC1, WHSC2, MIR943, TACC3, IDUA, C4orf48 for mental retardation; LETM1 y WHSC1 for microcephaly and KIAA1530 for growth retardation.

Genome-wide linkage scan for an ethnic Han Chinese pedigree affected with schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To perform genome-wide linkage analysis for an ethnic Han Chinese pedigree with schizophrenia in order to locate the susceptibility genes.</p><p><b>METHODS</b>Genomic DNA was extracted from 4 mL of peripheral blood using conventional phenol-chloroform method. Illumina Infinium Linkage 24 BeadChips chip was used for determining the genotypes through detection of single nucleotide polymorphisms (SNPs). After processing the raw data using Illumina BeadStudio software, two-point nonparametric linkage analysis and two-point parametric linkage analysis were performed with Merlin software.</p><p><b>RESULTS</b>By two-point nonparametric linkage analysis, 27 sites with high LOD scores (LOD=0.63-0.75, P U+003C 0.05) were identified. Among these, 3 SNPs(rs993694, rs992690 rs1861577) were located in 12p12.3 region, whilst the remainders were located in 4p12-q22 region. Two-point parametric linkage analysis under a dominant model has yielded almost identical results.</p><p><b>CONCLUSION</b>Chromosomal regions 4p12-q22 and 12p12.3 probably contain susceptibility genes for schizophrenia.</p>

Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight

The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candidate genes within linkage regions to identify genetic variants that predispose individuals to being overweight and developing type 2 diabetes. Through fine-mapping analysis of chromosome 4q34-35, we detected a locus potentially linked (nonparametric linkage 2.81, logarithm of odds 2.27, P=6 x 10-4) to type 2 diabetes in overweight or obese individuals (body mass index, BMI> or =23 kg m-2). Multiple regression analysis with type 2 diabetes-related phenotypes revealed a significant association (false discovery rate (FDR) P=0.006 for rs13144140; FDR P=0.002 for rs6830266) between GPM6A (rs13144140) and BMI and waist-hip ratio, and between NEIL3 (rs6830266) and insulin level from 1314 normal individuals. Our systematic search of genome-wide linkage and association studies, demonstrate that a linkage peak for type 2 diabetes on chromosome 4q34-35 contains two type 2 diabetes-related genes, GPM6A and NEIL3.

Two Cases of Partial Trisomy 4p and Partial Trisomy 14q

We present clinical and cytogenetic data on 2 cases of partial trisomy 4p and partial trisomy 14q. Both patients had an extra der(14)t(4;14)(p15.31;q12) chromosome due to a 3:1 segregation from a balanced translocation carrier mother. Array analyses indicated that their chromosomal breakpoints were similar, but there was no relationship between the 2 families. Both patients showed prominent growth retardation and psychomotor developmental delay. Other phenotypic manifestations were generally mild and variable; for example, patient 1 had a short palpebral fissure and low-set ears whereas patient 2 had a round face, asymmetric eyes, small ears, a short neck, finger/toe abnormalities, and behavioral problems.