Congenital renal diabetes insipidus caused by aquaporin 2 gene mutation in siblings: 2 cases report and literature review / 中国综合临床

Objective:To improve clinicians' understanding of congenital nephrogenital diabetes insipidus (CNDI) and to reduce missed and misdiagnosis. Methords 　Based on the literature, the clinical data and gene mutation of 2 patients with CNDI who were admitted to the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Henan University of Science and Technology on July 30, 2020 were analyzed retrospectively. Results:(1) The presentee, 4 years old, had irritable thirst, polydipsia and polyuria for more than 3 years. The sister, 2.5 years old, had irritable thirst, polydipsia and polyuria for more than 2 years. The clinical diagnosis was “CNDI”, and the symptoms improved after treatment with hydrochlorothiazide. (2) The genetic test revealed that the congenital nephrogenic uremia and her sister had a heterozygous mutation of c.170A>C (p.Q57P) and c.211G>A (p.Vl71M) in the aquaporin-2 gene, and the mother carried the AQP2 gene. c.170A>C(p.Q57P) mutation.Conclusion:CNDI is a rare disease. Early diagnosis and treatment can improve the prognosis of patients to the greatest extent, and prenatal diagnosis can guide eugenics.

A family study of autosomal recessive primary familial brain calcification caused by JAM2 gene mutation and literature review / 中华神经科杂志

Objective:To improve the clinician′s recognition of the clinical and molecular characteristics of primary familial brain calcification (PFBC).Methods:The detailed clinical information, imaging and molecular characteristics were analyzed in proband and family members of a genetically confirmed autosomal recessive PFBC family. The clinical and imaging features of junctional adhesion molecule 2 (JAM2) gene related PFBC were analyzed in combination with the literature review.Results:The proband was a 32-year-old man, with slurred speech and paroxysmal limb twitch as the first symptoms, accompanied by cognitive dysfunction, and rigidity in the limbs, with epilepsy in the past. Brain CT showed extensive, symmetrical, and bilateral calcification involving the cerebellum, basal ganglia, thalamus, subcortex and cortex. Other family members showed no related clinical symptoms. Brain CT of the parents of the proband showed no calcification. Gene testing of the proband revealed a homozygous c.685C>T(p.R229*) mutation in JAM2 gene, which has been reported as a pathogenic variation abroad, whereas has not been reported in China. The proband′s parents and children were found with heterozygous c.685C>T (p.R229*) mutation.Conclusions:Autosomal recessive inherited PFBC is a rare disease, and JAM2 mutation is a newly discovered pathogenic gene of PFBC in 2020. Patients with intracranial calcification should be alert of JAM2 gene mutation.

Spectrum analysis of gene mutations in retinitis pigmentosa and cone-rod dystrophy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the gene mutation spectrum of autosomal recessive retinitis pigmentosa(ARRP)pedigrees and cone-rod dystrophy(CORD)pedigrees in Ningxia region of China. <p>METHODS:Totally 35 ARRP pedigrees and 18 CORD pedigrees were included in Ningxia Eye Hospital from September 2016 to February 2020. Peripheral venous blood samples of the proband were collected for targeted capture enrichment and high-throughput sequencing using a genetic retinal disease capture chip that contain 232 pathogenic genes. Online analysis software was used to predict the pathogenicity of suspicious gene variation, and Sanger sequencing was used to analyze the co-segregation of the family members. <p>RESULTS: Totally 16 pathogenic genes were confirmed in 35 ARRP pedigrees, the mutations rate of RP1 gene was the highest, accounting for 14%(5/35), following were ABCA4, CRB1 and EYS gene, accounted for 11%(4/35); 18 CORD pedigrees carried 10 pathogenic genes. The mutation rate of ABCA4 gene was the highest, accounting for 28%(5/18), followed by ALMS1, PROM1, RPE65, USH2A gene, accounting for 11%(2/18). There were 5 co-exist disease-causing genes in ARRP and CORD pedigrees, which were ABCA4, CLN3, CRB1, PROM1, NRL, accounting for 42%(22/53).<p>CONCLUSION: There are similarities and crossover in the phenotype of ARRP and CORD. The pathogenic genes were overlaped. The most common overlaping gene between the two diseases is ABCA4.

Analysis of MYO7A gene mutation in a family with non-syndromic autosomal recessive deafness / 中华医学遗传学杂志

Objective@#To explore the genetic basis for a family with non-syndromic autosomal recessive deafness.@*Methods@#The proband and her parents were subjected to physical and audiological examinations. With genomic DNA extracted from peripheral blood samples, next-generation sequencing was carried out using a panel for deafness genes. Suspected mutation was validated by Sanger sequencing and qPCR analysis of her parents.@*Results@#The proband presented bilateral severe sensorineural hearing loss at three days after birth. Her auditory threshold was 110-120 dBnHL but with absence of vestibular and retinal symptoms. Her brother also had deafness but her parents were normal. No abnormality was found upon physical examination of her family members, while audiological examination showed no middle ear or retrocochlear diseases. Next-generation sequencing identified compound heterozygous mutations of the MYO7A gene, including a previously known c. 462C>A (p. Cys154Ter) and a novel EX43_46 Del, which were respectively derived from her mother and father.@*Conclusion@#The compound heterozygous mutations of the MYO7A gene probably underlie the disease in this family. Our findings has enriched the mutation spectrum for non-syndromic autosomal recessive deafness 2.

Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common Homozygous SLC4A1 Mutation in Two Lao Families

Primary distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows marked difference in inheritance patterns and clinical features in different parts of the world. While the disease shows autosomal dominant inheritance without any red cell morphological abnormalities in the temperate countries, it is almost invariably recessive, and often accompanies red cell morphological abnormalities or hemolytic anemia in the tropics, especially in Southeast Asia. Here, we report three patients with autosomal recessive (AR) dRTA, presenting with typical findings of failure to thrive and rickets, from two unrelated Lao families. The mutational analyses revealed that all three patients harbored the same homozygous SLC4A1 mutation, p.Gly701Asp. Adequate supplementation of alkali and potassium resulted in remarkable improvement of growth retardation and skeletal deformities of the patients. This is the first case report of Lao patients with AR dRTA caused by SLC4A1 mutations.

Research progress in related gene of autosomal recessive cutis laxa / 天津医药

@#Autosomal recessive cutis laxa is a common type of hereditary cutis laxa. Its pathogenesis is not completely clear, but involved genes and their corresponding functions and signaling pathways have gradually become the research focus. According to the latest research, the related genes and their responding signaling pathways not only provide a solid foundation for the pathogenesis of cutis laxa, but also indicate a direction for instructing healthy pregnancy and scientific nurture. This paper aims to review the recent advances in pathogenic genes and potential signaling pathways in autosomal recessive cutis laxa.

Correcting false-positive pathogenic categorization of benign variants by re-sequencing of the recessive deafness genes in carriers / 上海交通大学学报（医学版）

Objective· To correct the false-positive categorization of the rare and benign variants by re-sequencing of the recessive deafness genes in carriers. Methods · Heterozygous carriers of known causative mutations in recessive deafness genes were identified from normal hearing relatives of the deaf probands.Targeted next-generation sequencing was performed in those carriers to identify additional variants in trans,which was presumed to be benign. Results · A total of 30 normal-hearing carriers of heterozygous and known pathogenic mutations were identified. By targeted next-generation sequencing of corresponding genes,32 non-synonymous variants in trans were identified,which were categorized to benign mutations under the recessive and full-penetrant mode.Among those variants p.A434T in SLC26A4,p.R266Q in LOXHD1,p.K96Q in MYO15A,p.T123N in GJB2 and pV1299I in CDH23 were five rare variants with minor allele frequency of less than 0.005.Some of the 5 variants were predicted to be pathogenic by prediction programs including Polyphen-2, PROVEAN, SIFT and MutationTaster, or documented to be pathogenic by Deafness Variation Database or Human Genome Mutation Database. Conclusion · Re-sequencing of the recessive deafness genes in carriers may efficiently correct the false-positive categorization of some rare and benign variants to improve the accuracy and efficiency of the next-generation sequencing in diagnosis of monogenic recessive hereditary disorders.

Síndrome de Coffin-Siris / Coffin­Siris syndrome

El presente estudio describe un caso de un niño de 6 años 9 meses de edad, atendido en el Centro de De-sarrollo Infantil de la Universidad de Cuenca (CEDIUC), con las características del Síndrome de Coffin ­Siris. El cariotipo 46xy, inv9 (p12q13), determinó por rasgos clíni-cos, el diagnóstico de Síndrome de Coffin ­Siris.Niño producto de cuarta gesta; antecedentes prena-tales: amenaza de aborto; antecedentes natales: nace a las 38.4 semanas de gestación con un diagnóstico de distrés respiratorio, por lo cual estuvo internado durante 15 días en la Unidad de Cuidados intensivos de la clínica Humanitaria; antecedentes post-natales: presentó retraso global en el desarrollo, además de otras afec-taciones como cardiopatía congénita, comunicación interventricular. Recibe tratamiento en varios Centros.El síndrome de Coffin-Siris es una enfermedad genética rara, con baja incidencia por lo que es poco estudiada, caracterizada por retardo mental, retraso en el desarro-llo psicomotor, facies toscas, pelo ralo e hipoplasia de la uña del quinto dedo.Se realizó una exhaustiva revisión bibliográfica, encon-trándose que el síndrome de Coffin-Siris es una enfer-medad genética poco frecuente; existen alrededor de 10 casos publicados en Latinoamérica; la etiología aún está en controversia, no ha podido definirse su localización cromosómica, pero algunos autores han plantea-do una posible herencia autosómica recesiva.

This study describes a case of a 6-years and 9-months-old child, who was attended at the Child Develop-ment Center of the University of Cuenca (CEDIUC), with the characteristics of the Coffin-Syndrome. The karyoty-pe 46xy, inv9 (p12q13), determined by clinical features the diagnosis of Coffin-Syndrome.Child product of the fourth pregnancy, prenatal history: threatened abortion; natal history: he born at 38.4 wee-ks of gestation with a diagnosis of respiratory distress, for this reason he was hospitalized for 15 days in the In-tensive Care unit of the Humanitarian clinic; post-natal history: he presented global developmental delay, in addition to other affections such as congenital heart di-sease and ventricular septal defect. He receives treat-ment in several centers.The Coffin-Siris syndrome is a rare genetic disease, with a low incidence and for this reason it is not studied enou-gh, it is characterized by mental retardation, delayed psychomotor development, coarse facies, thinning hair and hypoplasia of the fifth finger nail.A comprehensive bibliographic review was performed, and Coffin-Siris syndrome is a rare genetic disease with about 10 cases published in Latin America; the etiolo-gy is still controversial, its chromosomal location has not been defined, but some authors have raised a possible autosomal recessive inheritance.