Population-based FMR1 carrier screening among reproductive women.

PURPOSE: Fragile X syndrome (FXS) is a neurodevelopmental disorder, caused by an CGG repeat expansion (FM, > 200 CGG) in the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Female carriers of a premutation (PM; 55-200 CGG) can transmit the PM allele, which, depending on the CGG allele size, can expand to an allele in the FM range in the offspring. METHODS: Carrier screening for FMR1 PM is not available in Thailand. This study aimed to investigate the prevalence of PM carriers among Thai reproductive women at the tertiary hospital. A total of 1250 females participated in this study; ages ranged from 20 to 45 years, mean of 30 years (S.D. = 6.27). RESULTS: Two carriers of a premutation allele, with 32,62 and 32,69 CGG repeats respectively, were identified. This corresponds to 1 in 600 women or 0.17% of the population. Further, three women carrying a gray zone allele (45-54 CGG repeats) were identified (29,51; 29,49; and 30,47 CGG repeats) which equals to 1:400 women or 0.25% of the population. No FM case was detected. CONCLUSIONS: This study heightens the importance of PM carrier screening of women of reproductive age, particularly for the higher risk of developing fragile X-associated primary ovarian insufficiency (FXPOI). Early identification of PM carrier status enhances family planning and fecundity alternatives and improves reproductive health outcomes leading to a better life.

Successful Treatment of Schwartz-Jampel Syndrome with Botulinum Toxin Type A.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive disorder characterized by typical facial dysmorphism, generalized muscle stiffness, joint contracture, and skeletal abnormalities. This condition is caused by mutations in the heparan sulfate proteoglycan 2 (HSPG2) gene, which encodes perlecan, a component of the basement membrane. The management of patients with SJS primarily aims to alleviate symptoms related to muscle stiffness. In this report, we describe a male patient with SJS type 1A. Trio whole-exome sequencing identified a pathogenic mutation (NM_001291860.1: c.10897C>T; p.Arg3633Ter) and variants of unknown significance (NM_001291860.2: c.413+10G>T). The patient experienced difficulty in opening his eyes and mouth, which significantly limited his daily activities. Botulinum toxin A injection was administered and demonstrated significant clinical improvement after the treatment.

Epileptic spasms related to neuronal differentiation factor 2 (NEUROD2) mutation respond to combined vigabatrin and high dose prednisolone therapy.

BACKGROUND: Epileptic spasms are a devastating form of early infantile epileptic encephalopathy (EIEE) with various etiologies. Early diagnosis and a shorter lead time to treatment are crucial to stop the seizures and optimize the neurodevelopmental outcome. Genetic testing has become an integral part of epilepsy care that directly guides management and family planning and discovers new targeted treatments. Neuronal differentiation Factor 2 (NEUROD2) variants have recently been a cause of neurodevelopmental disorders (NDDs) and EIEEs with distinctive features. However, there is limited information about the clinical and electroencephalographic response of epileptic spasm treatment in NEUROD2-related NDD syndrome. CASE PRESENTATION: We report a female patient of Southeast Asian ethnicity with global developmental delay and epileptic spasms commencing in the first few months of life. A novel de novo heterozygous pathogenic NEUROD2 variant, p. E130Q, was subsequently identified by whole-exome sequencing. Electroencephalogram before treatment showed multifocal independent spikes predominantly in both posterior head regions and demonstrated marked improvement following combined vigabatrin and high-dose prednisolone treatment. However, multiple courses of relapse occurred after weaning off the antiseizure medication. CONCLUSIONS: We propose that epileptic spasms related to de novo NEUROD2 pathogenic variant respond well to combined vigabatrin and high-dose prednisolone therapy. These findings may imply the benefit of using combination therapy to treat epileptic spasms in NEUROD2-related NDD syndrome.

Genomic findings of hypertrophic and dilated cardiomyopathy characterized in a Thai clinical genetics service.

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most common referrals in the Inherited Cardiovascular Condition (ICC) Genetics Service. Several issues must be discussed with patients and their families during the genetic consultation session, including the options for genetic testing and cardiovascular surveillance in family members. We developed an ICC registry and performed next-generation-based DNA sequencing for all patients affected by non-syndromic HCM and idiopathic DCM in our joint specialist genetics service. The target gene sequencing panel relied on the Human Phenotype Ontology with 237 genes for HCM (HP:0001639) and 142 genes for DCM (HP:0001644). All subjects were asked to contact their asymptomatic first-degree relatives for genetic counseling regarding their risks and to initiate cardiovascular surveillance and cascade genetic testing. The study was performed from January 1, 2014, to December 31, 2020, and a total of 62 subjects (31-HCM and 31-DCM) were enrolled. The molecular detection frequency was 48.39% (32.26% pathogenic/likely pathogenic, 16.13% variant of uncertain significance or VUS for HCM, and 25.81% (16.13% pathogenic/likely pathogenic, 9.68% VUS) for DCM. The most prevalent gene associated with HCM was MYBPC3. The others identified in this study included ACTN2, MYL2, MYH7, TNNI3, TPM1, and VCL. Among the DCM subjects, variants were detected in two cases with the TTN nonsense variants, while the others were missense and identified in MYH7, DRSP3, MYBPC3, and SCN5A. Following the echocardiogram surveillance and cascade genetic testing in the asymptomatic first-degree relatives, the detection rate of new cases was 8.82% and 6.25% in relatives of HCM and DCM subjects, respectively. Additionally, a new pre-symptomatic relative belonging to an HCM family was identified, although the genomic finding in the affected case was absent. Thus, ICC service is promising for the national healthcare system, aiming to prevent morbidity and mortality in asymptomatic family members.

Amelioration of osteogenesis in iPSC-derived mesenchymal stem cells from osteogenesis imperfecta patients by endoplasmic reticulum stress inhibitor.

AIM: Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder primarily caused by mutations in COL1A1 or COL1A2, which encode type I collagen. These mutations affect the quantity and/or quality of collagen composition in bones, leading to bone fragility. Currently, there is still a lack of treatment that addresses disease-causing factors due to an insufficient understanding of the pathological mechanisms involved. MAIN METHODS: Induced pluripotent stem cells (iPSCs) were generated from OI patients with glycine substitution mutations in COL1A1 and COL1A2 and developed into mesenchymal stem cells (iPS-MSCs). OI-derived iPS-MSCs underwent in vitro osteogenic induction to study cell growth, osteogenic differentiation capacity, mRNA expression of osteogenic and unfolded protein response (UPR) markers and apoptosis. The effects of 4-phenylbutyric acid (4-PBA) were examined after treatment of OI iPS-MSCs during osteogenesis. KEY FINDINGS: OI-derived iPS-MSCs exhibited decreased cell growth and impaired osteogenic differentiation and collagen expression. Expression of UPR genes was increased, which led to an increase in apoptotic cell death. 4-PBA treatment decreased apoptotic cells and reduced expression of UPR genes, including HSPA5, XBP1, ATF4, DDIT3, and ATF6. Osteogenic phenotypes, including RUNX2, SPP1, BGLAP, and IBPS expression, as well as calcium mineralization, were also improved. SIGNIFICANCE: MSCs differentiated from disease-specific iPSCs have utility as a disease model for identifying disease-specific treatments. In addition, the ER stress-associated UPR could be a pathogenic mechanism associated with OI. Treatment with 4-PBA alleviated OI pathogenesis by attenuating UPR markers and apoptotic cell death.

Clinical utility of combined preimplantation genetic testing methods in couples at risk of passing on beta thalassemia/hemoglobin E disease: A retrospective review from a single center.

Thalassemia and hemoglobinopathy is a group of hereditary blood disorder with diverse clinical manifestation inherited by autosomal recessive manner. The Beta thalassemia/Hemoglobin E disease (HbE/ßthal) causes a variable degree of hemolysis and the most severe form of HbE/ßthal disease develop a lifelong transfusion-dependent anemia. Preimplantation genetic testing (PGT) is an established procedure of embryo genetic analysis to avoid the risk of passing on this particular condition from the carrier parents to their offspring. Preimplantation genetic testing for chromosomal aneuploidy (PGT-A) also facilitates the selection of embryos without chromosomal aberration resulting in the successful embryo implantation rate. Herein, we study the clinical outcome of using combined PGT-M and PGT-A in couples at risk of passing on HbE/ßthal disease. The study was performed from January 2016 to December 2017. PGT-M was developed using short tandem repeat linkage analysis around the beta globin gene cluster and direct mutation testing using primer extension-based mini-sequencing. Thereafter, we recruited 15 couples at risk of passing on HbE/ßthal disease who underwent a combined total of 22 IVF cycles. PGT was performed in 106 embryos with a 3.89% allele drop-out rate. Using combined PGT-M and PGT-A methods, 80% of women obtained satisfactory genetic testing results and were able to undergo embryo transfer within the first two cycles. The successful implantation rate was 64.29%. PGT accuracy was evaluated by prenatal and postnatal genetic confirmation and 100% had a genetic status consistent with PGT results. The overall clinical outcome of successful live birth for couples at risk of producing offspring with HbE/ßthal was 53.33%. Conclusively, combined PGT-M and PGT-A is a useful technology to prevent HbE/ßthal disease in the offspring of recessive carriers.

Novel PANK2 mutation discovered among South East Asian children living in Thailand affected with pantothenate kinase associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is linked to brain iron accumulation caused by PANK2 gene mutation. Despite the importance of genetic testing to confirm PKAN and identify at risk parents, genetic screening is financially burdensome for developing countries like Thailand. Because genetic screeners are expensive and not reimbursed by the universal health care coverage system, they are not typically performed. To investigate clinical symptoms, radiological findings and mutation analysis for patients based in Thailand with unknown genetic status but suspected PKAN based on clinical symptoms. Genetic testing was performed for cases suspected for PKAN and their biological parents by direct genomic sequencing of PANK2 at Maharat Nakhon Ratchasima Hospital during 2017-2018. Clinical evaluation and documentation were performed by pediatric neurologists. Five children had classical onset form of PKAN. Most presented with gait dystonia. Three patients diagnosed after 4 years showed the eye-of-the-tiger sign in their brain MRI, whereas two younger patients revealed only isolated hyperintensity bilateral globus pallidus. However, PANK2 mutations were identified in all cases: the most common mutation was c.982-1G>C. This mutation was detected in four unrelated individuals but not reported in other studies. Genetic testing is recommended to confirm diagnoses in cases with supporting clinical features of PKAN with or without the classical 'eye-of-the-tiger-sign'. A novel PANK2 mutation (c.982-1G>C) was identified in South East Asian populations based in Thailand, suggesting that this genetic variant is a founder genotype in this population. Moreover, genetic diagnosis is helpful to provide appropriate genetic counseling to families.

Oral manifestations in patients and dogs with mucopolysaccharidosis Type VII.

Mucopolysaccharidosis Type VII (MPS7, also called ß-glucuronidase deficiency or Sly syndrome; MIM 253220) is an extremely rare autosomal recessive lysosomal storage disease, caused by mutations in the GUSB gene. ß-glucuronidase (GUSB) is a lysosomal hydrolase involved in the stepwise degradation of glucuronic acid-containing glycosaminoglycans (GAGs). Patients affected with MPS VII are not able to completely degrade glucuronic acid-containing GAGs, including chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, and heparan sulfate. The accumulation of these GAGs in lysosomes of various tissues leads to cellular and organ dysfunctions. Characteristic features of MPS VII include short stature, macrocephaly, hirsutism, coarse facies, hearing loss, cloudy cornea, short neck, valvular cardiac defects, hepatosplenomegaly, and dysostosis multiplex. Oral manifestations in patients affected with MPS VII have never been reported. Oral manifestations observed in three patients consist of wide root canal spaces, taurodontism, hyperplastic dental follicles, malposition of unerupted permanent molars, and failure of tooth eruption with malformed roots. The unusual skeletal features of the patients include maxillary hypoplasia, hypoplastic midface, long mandibular length, mandibular prognathism, hypoplastic and aplastic mandibular condyles, absence of the dens of the second cervical vertebra, and erosion of the cortex of the lower border of mandibles. Dogs affected with MPS VII had anterior and posterior open bite, maxillary hypoplasia, premolar crowding, and mandibular prognathism. Unlike patients with MPS VII, the dogs had unremarkable mandibular condyles. This is the first report of oral manifestations in patients affected with MPS VII.

A Novel PRKAR1A Mutation Identified in a Patient with Isolated Primary Pigmented Nodular Adrenocortical Disease.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome, especially the isolated form without Carney complex, associated with germline mutations in PRKAR1A, the protein kinase A regulatory subunit type 1 alpha gene. We report a 31-year-old female who presented with secondary amenorrhea, cushingoid appearance, and hypertension without Carney complex. Biochemical laboratory examinations confirmed the ACTH-independent adrenal Cushing syndrome with negative Liddle test. A small right adrenal adenoma of 0.8 cm was shown on computed tomography while magnetic resonance imaging revealed nodularity of both adrenal glands. The histological report confirmed PPNAD using laparoscopic right adrenalectomy, and subsequent left adrenalectomy was performed 6 months later. She had inherited heterozygosity of a novel germline mutation of the PRKAR1A gene (g.114213T≥G or c.709-5T≥G). This splice site mutation results in exon 8 skipping. Her father carrying the same mutation had no clinical features of either PPNAD or Carney complex. This novel PRKAR1A gene mutation, c.709-5T≥G, is reported here for the first time manifesting as an incomplete clinical expression of the isolated form of PPNAD and being inherited with low penetrance unlike other inherited mutations of the Carney complex which have a penetrance of almost 100%.

Exome sequencing for simultaneous mutation screening in children with hemophagocytic lymphohistiocytosis.

In the present study, we used exome sequencing to analyze PRF1, UNC13D, STX11, and STXBP2, as well as genes associated with primary immunodeficiency disease (RAB27A, LYST, AP3B1, SH2D1A, ITK, CD27, XIAP, and MAGT1) in Thai children with hemophagocytic lymphohistiocytosis (HLH). We performed mutation analysis of HLH-associated genes in 25 Thai children using an exome sequencing method. Genetic variations found within these target genes were compared to exome sequencing data from 133 healthy individuals. Variants identified with minor allele frequencies <5% and novel mutations were confirmed using Sanger sequencing. Exome sequencing data revealed 101 non-synonymous single nucleotide polymorphisms (SNPs) in all subjects. These SNPs were classified as pathogenic (n = 1), likely pathogenic (n = 16), variant of unknown significance (n = 12), or benign variant (n = 72). Homozygous, compound heterozygous, and double-gene heterozygous variants, involving mutations in PRF1 (n = 3), UNC13D (n = 2), STXBP2 (n = 3), LYST (n = 3), XIAP (n = 2), AP3B1 (n = 1), RAB27A (n = 1), and MAGT1 (n = 1), were demonstrated in 12 patients. Novel mutations were found in most patients in this study. In conclusion, exome sequencing demonstrated the ability to identify rare genetic variants in HLH patients. This method is useful in the detection of mutations in multi-gene associated diseases.

First successful trial of preimplantation genetic diagnosis for pantothenate kinase-associated neurodegeneration.

PURPOSE: We aim to present a case of a healthy infant born after intracytoplasmic sperm injection-in vitro fertilization (ICSI-IVF) with a preimplantation genetic diagnosis (PGD) for pantothenate kinase-associated neurodegeneration (PKAN) due to PANK2 mutation. METHODS: ICSI-IVF was performed on a Thai couple, 34-year-old female and 33-year-old male, with a family history of PKAN in their first child. Following fertilization, each of the embryos were biopsied in the cleavage stage and subsequently processed for whole-genome amplification. Genetic status of the embryos was diagnosed by linkage analysis and direct mutation testing using primer extension-based mini-sequencing. Comprehensive chromosomal aneuploidy screening was performed using a next-generation sequencing-based strategy. RESULTS: Only a single cycle of ICSI-IVF was processed. There were seven embryos from this couple-two were likely affected, three were likely carriers, one was likely unaffected, and one failed in target genome amplification. Aneuploidy screening was performed before making a decision on embryo transfer, and only one unaffected embryo passed the screening. That embryo was transferred in a frozen thawed cycle, and the pregnancy was successful. The diagnosis was confirmed by amniocentesis, which presented with a result consistent with PGD. At 38 weeks of gestational age, a healthy male baby was born. Postnatal genetic confirmation was also consistent with PGD and the prenatal results. At the age of 24 months, the baby presented with normal growth and development lacking any neurological symptoms. CONCLUSIONS: We report the first successful trial of PGD for PKAN in a developing country using linkage analysis and mini-sequencing in cleavage stage embryos.

Low oxygen saturation and severe anemia in compound heterozygous Hb Louisville [ß42(CD1)Phe→Leu] and Hb La Desirade [ß129(H7)Ala→Val].

OBJECTIVE: To investigate the cause(s) of a Thai male proband presenting low oxygen saturation by pulse oximetry (SpO2) and severe anemia. METHODS: As Hb variant was suspected, Hb typing was determined by high-performance liquid chromatography and capillary electrophoresis, and subsequently Hb variant was identified by DNA sequencing. Complete blood counts were performed using automated blood cell counter and oxygen saturation was measured by pulse oximetry. RESULTS: Proband was compound heterozygous for Hb Louisville [ß42(CD1)Phe→Leu] and Hb La Desirade [ß129(H7)Ala→Val]. Of the proband's two sons, one was compound heterozygous for Hb Louisville and Hb E and the other for Hb La Desirade and Hb E. The former son had similar clinical features and laboratory findings with those of the proband while the latter showed had no abnormal clinical manifestations. CONCLUSION: This the first report of compound heterozygosity of Hb Louisville and Hb La Desirade in an individual of Southeast Asian ethnicity. Hb variant identification is crucial for genetic counseling and appropriate treatment in regions where hemoglobinopathies are common.

A Novel Mutation in Thyroid Peroxidase Gene Causing Congenital Goitrous Hypothyroidism in a German-Thai Patient.

Thyroid dyshormonogenesis is responsible for 10-15% of all cases of congenital hypothyroidism and is usually inherited. We report a 26-year-old German-Thai male with congenital hypothyroidism caused by a compound heterozygous mutation in the thyroid peroxidase (TPO) gene. He was diagnosed with congenital goitrous hypothyroidism at 4 months of age and had been treated with levothyroxine replacement therapy. His goiter size had increased due to poor compliance to treatment. Ultrasonography of the thyroid gland showed a pattern suspicious for malignancy. The patient later underwent near-total thyroidectomy. Pathologic examination results were consistent with a multinodular goiter and no malignancy. Genetic analyses by direct sequencing of the entire exons and flanking regions of the TPO gene were performed in the index case and family members. The analyses revealed a compound heterozygote of novel TPO mutation of c.1727C>T in exon 10 resulting in amino acid substitution (p.Ala576Val) and c.2268_2269insT in exon 13 causing a frameshift mutation which introduced a stop codon after the insertion site. The latter has been reported in Chinese subjects. However, there is no previous report of c.1727C>T mutation in the literature. We found the allele contained a novel exon 10 mutation inherited from the patient's German mother and an exon 13 mutation from his Thai father. Analysis using two bioinformatic software programs indicated that this variant was likely to cause damage in the resulting protein molecule. The present report emphasizes the importance of regular follow-up and patient compliance to levothyroxine replacement in patients with goitrous congenital hypothyroidism to avoid prolonged stimulation of thyroid tissue by thyroid-stimulating hormone.

FIRST IDENTIFICATION OF HEMOGLOBIN LANSINGRAMATHIBODI [α87(F8)His → Gln; CAC>CAG (HBA1: c.264C>G)] IN A THAI FAMILY WITH SPURIOUS HYPOXEMIA.

We report, for the first time, hemoglobin (Hb) Lansing-Ramathibodi [α87(F8)His → Gln; CAC>CAG (HBA1: c.264C>G)] in four members of a Thai family presented with low measured oxygen saturation by pulse oximetry (SpO2), with discrepancy between low SpO2 and normal calculated oxygen saturation by arterial blood gas analysis, and no cyanosis or methemoglobinemia. The causative mutation is located in HBA1 whereas in previous reports of Hb Lansing the mutation is on HBA2, including that in a Japanese individual. The index and a male sibling also co-inherited Hb Pakse, a non-deletional α-thalassemia 2, resulting in mild reticulocytosis. Correct Hb identification is crucial for genetic counselling and, thereby, avoiding unnecessary investigation and treatment for spurious hypoxemia.

Screening of Fabry disease in patients with end-stage renal disease of unknown etiology: the first Thailand study.

We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease (ESRD) of an unknown origin. Venous blood samples were collected from ESRD patients for biochemical and molecular studies. Alpha-galactosidase A (α-GAL A) screening was performed from dried-blood spots using fluorometry. Molecular confirmation was performed using DNA sequencing of the GLA gene. A total of 142 male and female patients were included in this study. Ten patients (7.04%) exhibited a significant decrease in α-GAL A activity. There were no definitive pathogenic mutations observed in the molecular study. However, four patients revealed a novel nucleotide variant at c.1 -10 C>T, which was identified as a benign variant following screening in the normal population. In conclusion, the α-GAL A assay utilizing dried-blood spots revealed a significant false positive rate. There was no definitive Fabry disease confirmed in Thai patients diagnosed with ESRD of unknown etiology.

Angiotensin-converting enzyme gene polymorphism in Thai patients with systemic lupus erythematosus.

OBJECTIVE: To determine the association between angiotensin-converting enzyme (ACE) I/D polymorphism and the presence of systemic lupus erythematosus (SLE) disease and lupus nephritis (LN), including the association with disease severity in a Thai population. METHOD: In this retrospective study, 187 SLE patients followed up for (at least) 7 years in a rheumatology clinic of an academic hospital were enrolled. Disease severity and damage score at diagnosis and every 6 months, including treatment outcome of the first episode of LN were retrieved from medical records. The ACE genotype of SLE patients were determined by polymerase chain reaction and compared with ACE genotype in 687 controls from a database of a Thai surveillance cohort. RESULT: There was an association between ACE I/D polymorphism and the presence of SLE disease and LN (P < 0.001). Unexpectedly, the prevalence of DD genotype in SLE patients was lower than controls (OR 0.44 [95% CI 0.23-0.84], P = 0.013). The prevalence of ID genotype was not different between SLE patients and controls (OR 1.44 [95%CI 0.93-2.24], P = 0.102), but was higher in LN patients compared to controls (OR 1.77 [95% CI 1.14-2.72], P = 0.01). However, the ACE I/D polymorphism is not associated with SLE disease severity, either in patients with or without nephritis. CONCLUSION: The DD genotype could not be used as a poor prognostic marker for SLE and LN susceptibility in a Thai population. However, ID genotype may be associated with risk to develop LN.

Fine-needle aspiration cytology of parathyroid carcinoma mimic hürthle cell thyroid neoplasm.

Background. Fine-needle aspiration (FNA) can cause misdiagnosis of cytomorphological findings between parathyroid and thyroid lesions. Case Presentation. A 31-year-old man presented with a palpable neck mass on the right thyroid lobe. FNA cytology was reported as intrathyroidal lymphoid hyperplasia. After 5 years, repeated FNA was done on the enlarged nodule with result of Hürthle cell lesion. Prior to right lobectomy, laboratories revealed elevated serum calcium and parathyroid hormone (PTH). Careful history taking revealed chronic knee pain and ossifying fibroma at the maxilla. Ultrasonography showed a 2.8 cm mass inferior to right thyroid lobe. Pathology from en bloc resection was parathyroid carcinoma and immunohistochemical study revealed positivity for PTH. Genetic analysis found somatic mutation of CDC73 gene in exon1 (c.70delG) which caused premature stop codon in amino acid 26 (p.Glu24Lysfs*2). The final diagnosis was hyperparathyroidism-jaw tumor syndrome. Conclusions. FNA cytology of parathyroid can mimic thyroid lesion. It is important to consider and correlate the entire information from clinical history, laboratory, imaging, and FNA.

Chromosome 22q11.2 deletion syndrome presenting as adult onset hypoparathyroidism: clues to diagnosis from dysmorphic facial features.

We report a 26-year-old Thai man who presented with hypoparathyroidism in adulthood. He had no history of cardiac disease and recurrent infection. His subtle dysmorphic facial features and mild intellectual impairment were suspected for chromosome 22q11.2 deletion syndrome. The diagnosis was confirmed by fluorescence in situ hybridization, which found microdeletion in 22q11.2 region. The characteristic facial appearance can lead to clinical suspicion of this syndrome. The case report emphasizes that this syndrome is not uncommon and presents as a remarkable variability in the severity and extent of expression. Accurate diagnosis is important for genetic counseling and long-term health supervision by multidisciplinary team.

Chromosome 20p inverted duplication deletion identified in a Thai female adult with mental retardation, obesity, chronic kidney disease and characteristic facial features.

We report on a 21-year-old Thai woman presenting with mental retardation, developmental delays, selective mutism, distinctive facial features, sensorineural hearing loss, single right kidney, uterine didelphys and obesity. A longitudinal clinical course beginning in childhood revealed excessive weight gain, poor language skills and poor school performance. Chronic kidney disease stage 4, with elevated blood pressure, was first noted in adulthood. Array comparative genomic hybridization detected a copy loss at 20p13 co-existing with a copy gain at 20p13-20p11.22. A conventional cytogenetic study revealed the complex structural rearrangement of chromosome 20 [der (20) dup (20) (p11.2p13) del (20) (p13.pter)]. A FISH analysis, using probes against duplication and deletion regions, confirmed that there was an inverted duplication of p11.2-p13 and a deletion in the subtelomere region. Previous reports have identified this cytogenetic characterization in a Caucasian boy. Therefore, this is the first reported case of chromosome 20p inverted duplication deletion syndrome in an adult from the Southeast Asian population group.