PMANet: a time series forecasting model for Chinese stock price prediction.

Forecasting stock movements is a crucial research endeavor in finance, aiding traders in making informed decisions for enhanced profitability. Utilizing actual stock prices and correlating factors from the Wind platform presents a potent yet intricate forecasting approach. While previous methodologies have explored this avenue, they encounter challenges including limited comprehension of interrelations among stock data elements, diminished accuracy in extensive series, and struggles with anomaly points. This paper introduces an advanced hybrid model for stock price prediction, termed PMANet. PMANet is founded on Multi-scale Timing Feature Attention, amalgamating Multi-scale Timing Feature Convolution and Ant Particle Swarm Optimization. The model elevates the understanding of dependencies and interrelations within stock data sequences through Probabilistic Positional Attention. Furthermore, the Encoder incorporates Multi-scale Timing Feature Convolution, augmenting the model's capacity to discern multi-scale and significant features while adeptly managing lengthy input sequences. Additionally, the model's proficiency in addressing anomaly points in stock sequences is enhanced by substituting the optimizer with Ant Particle Swarm Optimization. To ascertain the model's efficacy and applicability, we conducted an empirical study using stocks from four pivotal industries in China. The experimental outcomes demonstrate that PMANet is both feasible and versatile in its predictive capability, yielding forecasts closely aligned with actual values, thereby fulfilling application requirements more effectively.

Novel Germline KIT Variants in Families With Severe Piebaldism: Case Series and Literature Review.

INTRODUCTION: Piebaldism is a rare autosomal dominant disorder characterized by congenital white forelock and depigmented patches, which is most commonly caused by deleterious variants in the KIT gene. METHODS: Four KIT variants were identified in a piebaldism case series by whole-exome sequencing. Functional experiments, including in vitro minigene reporter assay and enzyme-linked immunosorbent assay, were carried out to elucidate the pathogenicity of the variants. The genotype-phenotype correlation was summarized through extensive literature reviewing. RESULTS: All the four cases had severe piebaldism presented with typical white forelock and diffuse depigmentation on the ventral trunk and limbs. Four germline variants at the tyrosine kinase (TK) domains of the KIT gene were identified: two novel variants c.1990+1G>A (p.Pro627_Gly664delinsArg) and c.2716T>C (p.Cys906Arg), and two known variants c.1879+1G>A (p.Gly592_Pro627delinsAla) and c.1747G>A (p.Glu583Lys). Both splicing variants caused exon skipping and inframe deletions in the TK1 domain. The missense variants resided at the TK1 and TK2 domains respectively impairing PI3K/AKT and MAPK/ERK signaling pathways, the downstream of KIT. All severe cases were associated with variants in the TK domains, eliciting a major dominant-negative mechanism of the disease. CONCLUSION: Our data expand the mutation spectrum of KIT, emphasized by a dominant-negative effect of variants in the critical TK domains in severe cases. We also share the experience of prenatal diagnosis and informed reproductive choices for the affected families.

Improving the Efficiency of CRISPR Ribonucleoprotein-Mediated Precise Gene Editing by Small Molecules in Porcine Fibroblasts.

The aim of this study was to verify whether small molecules can improve the efficiency of precision gene editing using clustered regularly interspaced short palindromic repeats (CRISPR) ribonucleoprotein (RNP) in porcine cells. CRISPR associated 9 (Cas9) protein, small guide RNA (sgRNA), phosphorothioate-modified single-stranded oligonucleotides (ssODN), and different small molecules were used to generate precise nucleotide substitutions at the insulin (INS) gene by homology-directed repair (HDR) in porcine fetal fibroblasts (PFFs). These components were introduced into PFFs via electroporation, followed by polymerase chain reaction (PCR) for the target site. All samples were sequenced and analyzed, and the efficiencies of different small molecules at the target site were compared. The results showed that the optimal concentrations of the small molecules, including L-189, NU7441, SCR7, L755507, RS-1, and Brefeldin A, for in vitro-cultured PFFs' viability were determined. Compared with the control group, the single small molecules including L-189, NU7441, SCR7, L755507, RS-1, and Brefeldin A increased the efficiency of HDR-mediated precise gene editing from 1.71-fold to 2.28-fold, respectively. There are no benefits in using the combination of two small molecules, since none of the combinations improved the precise gene editing efficiency compared to single small molecules. In conclusion, these results suggested that a single small molecule can increase the efficiency of CRISPR RNP-mediated precise gene editing in porcine cells.

CRISPR Ribonucleoprotein-Mediated Precise Editing of Multiple Genes in Porcine Fibroblasts.

The multi-gene editing porcine cell model can analyze the genetic mechanisms of multiple genes, which is beneficial for accelerating genetic breeding. However, there has been a lack of an effective strategy to simultaneously perform precise multi-gene editing in porcine cells. In this study, we aimed to improve the efficiency of CRISPR RNP-mediated precise gene editing in porcine cells. CRISPR RNP, including Cas9 protein, sgRNA, and ssODN, was used to generate precise nucleotide substitutions by homology-directed repair (HDR) in porcine fetal fibroblasts (PFFs). These components were introduced into PFFs via electroporation, followed by PCR for each target site. To enhance HDR efficacy, small-molecule M3814 and phosphorothioate-modified ssODN were employed. All target DNA samples were sequenced and analyzed, and the efficiencies of different combinations of the CRISPR RNP system in target sites were compared. The results showed that when 2 µM M3814, a small molecule which inhibits NHEJ-mediated repair by blocking DNA-PKs activity, was used, there was no toxicity to PFFs. The CRISPR RNP-mediated HDR efficiency increased 3.62-fold. The combination of CRISPR RNP with 2 µM M3814 and PS-ssODNs achieved an HDR-mediated precision gene modification efficiency of approximately 42.81% in mutated cells, a 6.38-fold increase compared to the control group. Then, we used the optimized CRISPR RNP system to perform simultaneous editing of two and three loci at the INS and RLN3 genes. The results showed that the CRISPR RNP system could simultaneously edit two and three loci. The efficiency of simultaneous editing of two loci was not significantly different from that of single-gene editing compared to the efficiency of single-locus editing. The efficiency of simultaneous precise editing of INS, RLN3 exon 1, and RLN3 exon 2 was 0.29%, 0.24%, and 1.05%, respectively. This study demonstrated that a 2 µM M3814 combination with PS-ssODNs improves the efficacy of CRISPR RNP-mediated precise gene editing and allows for precise editing of up to three genes simultaneously in porcine cells.

Single-Cell RNA Sequencing Reveals Differences in Chromatin Remodeling and Energy Metabolism among In Vivo-Developed, In Vitro-Fertilized, and Parthenogenetically Activated Embryos from the Oocyte to 8-Cell Stages in Pigs.

In vitro-fertilized (IVF) and parthenogenetically activated (PA) embryos, key to genetic engineering, face more developmental challenges than in vivo-developed embryos (IVV). We analyzed single-cell RNA-seq data from the oocyte to eight-cell stages in IVV, IVF, and PA porcine embryos, focusing on developmental differences during early zygotic genome activation (ZGA), a vital stage for embryonic development. (1) Our findings reveal that in vitro embryos (IVF and PA) exhibit more similar developmental trajectories compared to IVV embryos, with PA embryos showing the least gene diversity at each stage. (2) Significant differences in maternal mRNA, particularly affecting mRNA splicing, energy metabolism, and chromatin remodeling, were observed. Key genes like SMARCB1 (in vivo) and SIRT1 (in vitro) played major roles, with HDAC1 (in vivo) and EZH2 (in vitro) likely central in their complexes. (3) Across different types of embryos, there was minimal overlap in gene upregulation during ZGA, with IVV embryos demonstrating more pronounced upregulation. During minor ZGA, global epigenetic modification patterns diverged and expanded further. Specifically, in IVV, genes, especially those linked to H4 acetylation and H2 ubiquitination, were more actively regulated compared to PA embryos, which showed an increase in H3 methylation. Additionally, both types displayed a distinction in DNA methylation. During major ZGA, IVV distinctively upregulated genes related to mitochondrial regulation, ATP synthesis, and oxidative phosphorylation. (4) Furthermore, disparities in mRNA degradation-related genes between in vivo and in vitro embryos were more pronounced during major ZGA. In IVV, there was significant maternal mRNA degradation. Maternal genes regulating phosphatase activity and cell junctions, highly expressed in both in vivo and in vitro embryos, were degraded in IVV in a timely manner but not in in vitro embryos. (5) Our analysis also highlighted a higher expression of many mitochondrially encoded genes in in vitro embryos, yet their nucleosome occupancy and the ATP8 expression were notably higher in IVV.

Multiplexed Gene Engineering Based on dCas9 and gRNA-tRNA Array Encoded on Single Transcript.

Simultaneously, multiplexed genome engineering and targeting multiple genomic loci are valuable to elucidating gene interactions and characterizing genetic networks that affect phenotypes. Here, we developed a general CRISPR-based platform to perform four functions and target multiple genome loci encoded in a single transcript. To establish multiple functions for multiple loci targets, we fused four RNA hairpins, MS2, PP7, com and boxB, to stem-loops of gRNA (guide RNA) scaffolds, separately. The RNA-hairpin-binding domains MCP, PCP, Com and λN22 were fused with different functional effectors. These paired combinations of cognate-RNA hairpins and RNA-binding proteins generated the simultaneous, independent regulation of multiple target genes. To ensure that all proteins and RNAs are expressed in one transcript, multiple gRNAs were constructed in a tandemly arrayed tRNA (transfer RNA)-gRNA architecture, and the triplex sequence was cloned between the protein-coding sequences and the tRNA-gRNA array. By leveraging this system, we illustrate the transcriptional activation, transcriptional repression, DNA methylation and DNA demethylation of endogenous targets using up to 16 individual CRISPR gRNAs delivered on a single transcript. This system provides a powerful platform to investigate synthetic biology questions and engineer complex-phenotype medical applications.

Genetic subtypes and phenotypic characteristics of 110 patients with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a complex disorder caused by impaired paternally expressed genes on chromosome 15q11-q13. Variable findings have been reported about the phenotypic differences among PWS genetic subtypes. METHODS: A total of 110 PWS patients were diagnosed from 8,572 pediatric patients included from July 2013 to December 2021 by MLPA and MS-MLPA assays. Atypical deletions were defined by genomic CNV-sequencing. Maternal uniparental disomy (UPD) was subgrouped by microsatellite genotyping. Clinical data were collected for phenotype-genotype associations. Twenty-one patients received growth hormone (GH) treatment, and the anthropometric and laboratory parameters were evaluated and compared. RESULTS: Genetically, the 110 patients with PWS included 29 type I deletion, 56 type II deletion, 6 atypical deletion, 11 heterodisomy UPD, and 8 isodisomy UPD. The UPD group had significantly higher maternal age (31.4 ± 3.4 vs 27.8 ± 3.8 years), more anxiety (64.29% vs 26.09%) and autistic traits (57.14% vs 26.09%), and less hypopigmentation (42.11% vs 68.24%) and skin picking (42.86% vs 71.01%) than the deletion group. The type I deletion group was diagnosed at earlier age (3.7 ± 3.3 vs 6.2 ± 3.2 years) and more common in speech delay (95.45% vs 63.83%) than the type II. The isodisomy UPD group showed a higher tendency of anxiety (83.33% vs 50%) than the heterodisomy. GH treatment for 1 year significantly improved the SDS of height (- 0.43 ± 0.68 vs - 1.32 ± 1.19) and IGF-I (- 0.45 ± 0.48 vs - 1.97 ± 1.12). No significant changes were found in thyroid function or glucose/lipid metabolism. CONCLUSION: We explored the physical, psychological and behavioral phenotype-genotype associations as well as the GH treatment effect on PWS from a large cohort of Chinese pediatric patients. Our data might promote pediatricians' recognition and early diagnosis of PWS.

[NIPBL gene mutations in two children with Cornelia de Lange syndrome].

Both children (one boy and one girl) experienced disease onset in infancy and visited the hospital due to growth retardation. They had unusual facies including thick hair, arched and confluent eyebrows, long and curly eyelashes, short nose, and micrognathia. Patient 1 had congenital heart disease (atrial septal defect and pulmonary stenosis) and special dermatoglyph (a single palmar crease). Patient 2 had cleft palate and moderate-to-severe deafness. Clinical features suggested Cornelia de Lange syndrome in both children. High-throughput sequencing was used to detect the seven known pathogenic genes of Cornelia de Lange syndrome, i.e., the NIPBL, SMC1A, SMC3, HDAC8, RAD21, EP300, and ANKRD11 genes. Sanger sequencing was used to analyze and verify gene mutations. Both patients were found to have novel mutations in the NIPBL gene. One patient had a frameshift mutation in exon 45, c.7834dupA, which caused early termination of translation and produced truncated protein p.R2612fsX20. The other patient had a nonsense mutation, c.505C>T, which caused a premature stop codon and produced truncated protein Q169X. Such mutations were not found in their parents or 50 unrelated healthy individuals.

Contactin­associated protein­like 2 expression in SH­SY5Y cells is upregulated by a FOXP2 mutant with a shortened poly­glutamine tract.

The forkhead box protein P2 (FOXP2) gene encodes an important transcription factor that contains a polyglutamine (poly­Q) tract and a forkhead DNA binding domain. It has been observed that FOXP2 is associated with speech sound disorder (SSD), and mutations that decrease the length of the poly­Q tract were identified in the FOXP2 gene of SSD patients. However, the exact role of poly­Q reduction is not well understood. In the present study, constructs expressing wild­type and poly­Q reduction mutants of FOXP2 were generated by polymerase chain reaction (PCR) using lentiviral vectors and transfected into the SH­SY5Y neuronal cell line. Quantitative reverse transcription (qRT)­PCR and western blotting indicated that infected cells stably expressed high levels of FOXP2. Using this cell model, the impact of FOXP2 on the expression of contactin­associated protein­like 2 (CNTNAP2) were investigated, and CNTNAP2 mRNA expression levels were observed to be significantly higher in cells expressing poly­Q­reduced FOXP2. In addition, the expression level of CASPR2, a mammalian homolog of Drosophila Neurexin IV, was increased in cells expressing the FOXP2 mutant. Demonstration of regulation by FOXP2 indicates that CNTNAP2 may also be involved in SSD.

CNTNAP2 Is Significantly Associated With Speech Sound Disorder in the Chinese Han Population.

Speech sound disorder is the most common communication disorder. Some investigations support the possibility that the CNTNAP2 gene might be involved in the pathogenesis of speech-related diseases. To investigate single-nucleotide polymorphisms in the CNTNAP2 gene, 300 unrelated speech sound disorder patients and 200 normal controls were included in the study. Five single-nucleotide polymorphisms were amplified and directly sequenced. Significant differences were found in the genotype (P = .0003) and allele (P = .0056) frequencies of rs2538976 between patients and controls. The excess frequency of the A allele in the patient group remained significant after Bonferroni correction (P = .0280). A significant haplotype association with rs2710102T/+rs17236239A/+2538976A/+2710117A (P = 4.10e-006) was identified. A neighboring single-nucleotide polymorphism, rs10608123, was found in complete linkage disequilibrium with rs2538976, and the genotypes exactly corresponded to each other. The authors propose that these CNTNAP2 variants increase the susceptibility to speech sound disorder. The single-nucleotide polymorphisms rs10608123 and rs2538976 may merge into one single-nucleotide polymorphism.

CYP17A1 gene mutations and hypertension variations found in 46, XY females with combined 17α-hydroxylase/17, 20-lyase deficiency.

The aim of this study was to analyze the structural consequences of the mutations in CYP17A1 gene and their relationship with the variations of clinical manifestations in three patients who presented with complete or partial combined 17α-hydroxylase/17,20-lyase deficiency (17OHD). DNA sequences of the coding exons and intron/exon boundaries of the CYP17A1 gene were analyzed for mutations. In silico analysis with computational three-dimensional model of human P450c17 and multiple alignments analysis were performed to evaluate the spatial conformational changes by missense mutations. Five mutations p.S117fs (c.351_352delCT), p.H373L (c.1184 A>T), p.Y329fs (c.985_987delTACinsAA), p.A82D (c.245 C>A) and p.L209P (c.626 T>C) were identified in three patients, respectively. The novel mutation p.S117fs (c.351_352delCT) has not been reported previously. In silico analysis explained the conformational changes by the described mutations, which resulted in different severe 17OHD. Our studies also suggest that molecular data accompanying with in silico analysis of the CYP17A1 gene are much helpful for the diagnosis, management and genetic counseling of 17OHD.

[Molecular genetics of functional articulation disorder in children].

Genetic factors are an important cause of functional articulation disorder in children. This article reviews some genes and chromosome regions associated with a genetic susceptibility to functional articulation disorders. The forkhead box P2 (FOXP2) gene on chromosome 7 is introduced in details including its structure, expression and function. The relationship between the FOXP2 gene and developmental apraxia of speech is discussed. As a transcription factor, FOXP2 gene regulates the expression of many genes. CNTNAP2 as an important target gene of FOXP2 is a key gene influencing language development. Functional articulation disorder may be developed to dyslexia, therefore some candidate regions and genes related to dyslexia, such as 3p12-13, 15q11-21, 6p22 and 1p34-36, are also introduced. ROBO1 gene in 3p12.3, ZNF280D gene, TCF12 gene, EKN1 gene in 15q21, and KIAA0319 gene in 6p22 have been candidate genes for the study of functional articulation disorder.

Two novel mutations in the BCKDHB gene (R170H, Q346R) cause the classic form of maple syrup urine disease (MSUD).

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder that is caused by mutations in the subunits of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. BCKD is a mitochondrial complex encoded by four nuclear genes (BCKDHA, BCKDHB, DBT, and DLD) and is involved in the metabolism of branched-chain amino acids (BCAAs). In this study, we investigated the DNA sequences of BCKDHA, BCKDHB and DBT genes for mutations in a Chinese newborn with the classic form of MSUD and predicted the associated conformational changes using molecular modeling. We identified two previously unreported mutations in the BCKDHB gene, R170H (c.509G>A) in exon 5 and Q346R (c.1037 A>G) in exon 9. In silico analysis of the two novel missense mutations revealed that the mutation R170H-ß alters the spatial orientation with both Y195-ß' and S206-α, which results in unstable ß-ß' assembly and an unstable K(+) ion binding loop of the α subunit, respectively; The Q346R mutation is predicted to disrupt the spatial conformation between Q346-ß and I357-ß', which reduces the affinity of the ß-ß' subunits. These results indicate that R170-ß and Q346-ß are crucial for the activity of the E1 component. These two novel mutations, R170H and Q346R result in the patient's clinical manifestation of the classic form of MSUD.

Analysis of MECP2 gene copy number in boys with autism.

Autism is a severe neurodevelopmental disorder with a strong genetic basis.The methyl-CpG binding protein 2 gene (MECP2) is a dosage-sensitive gene in brain development and has been implicated as a candidate gene for autism. Duplication of the MECP2 gene has been reported in a few boys with autistic features. To further investigate the association of MECP2 duplication with autism, the authors performed real-time quantitative polymerase chain reaction (PCR) to detect copy number variations of the MECP2 gene in 82 autistic boys. No copy number variation was found in these patients, indicating that duplication of the MECP2 gene is not frequent in autistic patients. The authors consider that duplication of the MECP2 gene has no major effect on the susceptibility to autism. Replication of studies in a large-sized sample and a well-characterized subgroup of autism are warranted to further identify the association of MECP2 gene duplication with autism.

Three novel CYP17A1 gene mutations (A82D, R125X, and C442R) found in combined 17α-hydroxylase/17,20-lyase deficiency.

The aim of this study was to analyze the structure and functional consequences of 3 novel mutations (A82D, R125X, and C442R) of the CYP17A1 gene found in 2 patients with combined 17α-hydroxylase/17,20-lyase deficiency (17OHD). Two Chinese 46, XY female patients were diagnosed with 17OHD based on clinical findings and biochemical results. The CYP17A1 gene was analyzed by polymerase chain reaction direct sequencing. An in vitro expression system was performed in HEK293 cells to analyze the mutant P450c17 activity compared with the wild type. Analysis of the CYP17A1 gene sequences in patient 1 showed compound heterozygous mutations A82D (g.417 C > A) in exon 1 and Y329fs (g.4869 T > A, 4871del) in exon 6; DNA sequencing analysis in patient 2 revealed compound heterozygous mutations R125X (g.2045 C > T) in exon 2 and C442R (g.6457 T > C) in exon 8. The mutations A82D, R125X, and C442R have not been reported previously. The functional study demonstrated that the A82D, R125X, and C442R mutations almost completely eliminate enzymatic activity. These results, which indicate that Ala 82 and Cys 442 are crucial for both 17-hydroxylase and 17,20-lyase activities, help define the structure-function relationship of the CYP17A1 gene. The novel mutations A82D, R125X, and C442R further clarify the patients' clinical manifestations of combined 17OHD.

[Characteristics of developmental regression in autistic children].

OBJECTIVE: About 30% of autistic cases experience developmental regression around 2 years of age. The clinical course and manifestations of autistic children with regression remain unclear. This study investigated the clinical features of a group of autistic children with regression. METHODS: One hundred and fifty-two children at ages of 2.5-6.5 years confirmed with autism based on DSM-IV diagnostic criteria were enrolled. They were grouped according to language development: normal or regression. The perinatal history, developmental history and characteristics of regression were investigated. The symptoms were compared between the two groups. RESULTS: Regressions were observed in 33 children (21.7%) at age of between 16 and 21 months, with loss both in communicative skills and social engagement. The regressive group was scored significantly higher on the Childhood Autism Rating Scale (CARS) (P<0.05) and had a relatively higher proportion of severely ill children (66.7% vs 45.4%; P<0.05)compared with the non-regressive group. CONCLUSIONS: Regression as a characteristic symptom occurs in some autistic children and is of value for diagnosis of autism. The autistic children with regression display more severe social and language impairments than those without regression. Regressive autism may be a special subtype.

Association between FOXP2 gene and speech sound disorder in Chinese population.

AIM: FOXP2 was described as the first gene relevant to human speech and language disorders. The main objective of this study was to compare the distribution of FOXP2 gene polymorphisms between patients with speech sound disorder and healthy controls. METHODS: Five FOXP2 polymorphisms, rs923875, rs2396722, rs1852469, rs17137124 and rs1456031, were analyzed in 150 patients with speech sound disorder according to DSM-IV, as well as in 140 healthy controls. Coding exons for key domains of FOXP2 were also sequenced in all the patients. RESULTS: Significant differences in the genotype (P = 0.001) and allele (P = 0.0025) frequencies of rs1852469 (located 5' upstream of the ATG initiator codon) were found between patients and controls. The excess of the T allele in the patients group remained significant after Bonferroni correction (P = 0.0126). Further investigations revealed a risk haplotype: rs2396722T/+rs1852469T. Our screening of key domains did not detect any point mutations in this sample. But we detected heterozygous triplet deletion of the glutamine-encoding region of exon 5 that alter FOXP2 protein sequence in five probands. These changes are predicted to yield a polyglutamine tract reduction from 40 to 39 consecutive glutamines. CONCLUSIONS: Our data support a possible role of FOXP2 in the vulnerability to speech sound disorder, which adds further evidence to implicate this gene in speech and language functions.

[Comorbidities and behavioral problems in children with functional articulation disorder].

OBJECTIVE: To study the incidences of comorbidities and behavioral problems in children with functional articulation disorders. METHODS: One hundred and twelve children with functional articulation disorders (aged 4-11 years) were enrolled. Their comorbidities were identified based on clinical investigations and the DSM-IV diagnosis criteria of attention deficit hyperactivity disorder (ADHD), stuttering, tic disorders and enuresis. Behavioral problems were evaluated by the Conners Parent Symptom Questionnaire and the Child Behavior Checklist. RESULTS: Sixty-nine patients (61.6%) had one or more comorbidities. The incidence of comorbidity in children with middle-severe functional articulation disorders was higher than in those with mild disorders. The most common comorbidity was language impairment (30.4%), followed by stuttering (16.1%), enuresis (13.4%), and tic disorders (6.3%). In school age children, ADHD (47.5%) was the most common comorbidity. The incidence of behavioral problems was 40.2% by the Child Behavior Checklist and 57.1% by the Parent Symptom Questionnaire. CONCLUSIONS: The children with functional articulation disorders have high incidence of comorbidity and many behavioral problems.

[The investigation of the relationship between the phenotypes of 46, XX males and the SRY gene].

OBJECTIVE: To investigate the relationship between the phenotypes in XX male patients and the sex determining region(SRY) gene. METHODS: Multiple polymerase chain reactions were carried out in 6 male patients with karyotype of 46, XX, and then the PCR products were sequenced directly. RESULTS: Three cases of male infertility were positive for the SRY gene without evident malformation in their extra genitalia, while 3 cases with testes were negative for the SRY gene, with evident malformation in their extra genitalia. CONCLUSION: The SRY gene is key in sex determination and development, yet there might be other important genes involved.

MeCP2 gene mutation analysis in autistic boys with developmental regression.

Autism and Rett syndrome are both pervasive developmental disorders and share many characteristics in common. One of these features is developmental regression with loss of social, cognitive and language skills after a period of apparently normal development during the first 1-2 years of life, which raises the question of whether there is a common pathway underlying regression in these two disorders. The Rett syndrome gene was identified as MeCP2 gene on Xq28, a powerful transcriptional repressor. To explore its possible role in the etiology of autism and involvement in regression, we searched for MeCP2 gene mutations in a well characterized sample of 31 autistic boys with developmental regression by direct sequencing. One sequence variant in 3' untranslated region was observed. The patient inherited the variant from his unaffected mother, so it may be a rare polymorphism. No coding sequence variant was found in any of the patients tested. We conclude that mutations in the coding sequence of MeCP2 are not a frequent cause of regression in autism. The long 3' untranslated region of MeCP2 is highly conserved across species, suggesting that they are important for the post-transcriptional regulation of MeCP2 gene. It may be worthwhile extending the mutation screening, with a larger sample of strictly defined phenotype, to regulatory elements and untranslated regions of this gene, to explore to what degree MeCP2 gene is involved in the etiology of autism and its possible role in the regression of autism.