DLG3 Impairment Caused by Missense Variants in Non-Syndromic X-Linked Mental Retardation

X-lined intellectual disability (XLID), formerly known as X-lined mental retardation, is defined as genetically heterogeneous disorders with remarkable cognitive impairment and abnormal adaptive behaviour skills. This study demonstrates the Disc-large homolog 3 (DLG3) gene impairment in 2 different unrelated male probands. The results detected two missense mutations in the DLG3 gene, c.2267 G > A (p.Arg756Gln) and c.2359G > A p. (Gly787Ser) using by NGS. Both mutations were run in the PolyPhen2 program for mutation sensitivity check and showed to have 0.709 and 1, respectively. The familial transmission pattern of MR detected both mothers to be heterozygote. The mutations were shown to have caused non-syndromic XLMR (NS-XLMR) as both males did not show any abnormal facial or physiological features. Based on the IQ measurement, proband 1 and 2’ IQs were measured 40 and 33, and they were diagnosed with moderate and severe XLMR, respectively. Both affected males showed significant deterioration in neural development and behaviour abilities, which indicates the significant impact of the mutation on neurotransmitters and maintenance of NMDA receptors in neural functions. However, further molecular and functional studies are necessary to provide more conclusive evidence of the detailed abnormalities caused by the reported mutations.

Caloric Restriction in Group-Housed Mice: Littermate and Sex Influence on Behavioral and Hormonal Data

Much of the research done on aging, oxidative stress, anxiety, and cognitive and social behavior in rodents has focused on caloric restriction (CR). This often involves several days of single housing, which can cause numerous logistical problems, as well as cognitive and social dysfunctions. Previous results in our laboratory showed the viability of long-term CR in grouped rats. Our research has studied the possibility of CR in grouped female and male littermates and unrelated CB6F1/J (C57BL/6J × BALBc/J hybrid strain) mice, measuring: (i) possible differences in body mass proportions between mice in ad libitum and CR conditions (at 70% of ad libitum), (ii) aggressive behavior, using the number of pushes and chasing behavior time as an indicator and social behavior using the time under the feeder as indicator, and (iii) difference in serum adrenocorticotropic hormone (ACTH) concentrations (stress biomarker), under ad libitum and CR conditions. Results showed the impossibility of implementing CR in unrelated male mice. In all other groups, CR was possible, with a less aggressive behavior (measured only with the number of pushes) observed in the unrelated female mice under CR conditions. In that sense, the ACTH levels measured on the last day of CR showed no difference in stress levels. These results indicate that implementantion of long-term CR in mice can be optimized technically and also related to their well-being by grouping animals, in particular, related mice.

Kagami-Ogata Syndrome: Case Series and Review of Literature

Kagami-Ogata syndrome (KOS) (OMIM #608149) is a genetic imprinting disorder affecting chromosome 14 that results in a characteristic phenotype consisting of typical facial features, skeletal abnormalities including rib abnormalities described as “coat hanger ribs,” respiratory distress, abdominal wall defects, polyhydramnios, and developmental delay. First identified by Wang et al in 1991, over 80 cases of KOS have been reported in the literature. KOS, however, continues to remain a rare and potentially underdiagnosed disorder. In this report, we describe two unrelated male infants with differing initial presentations who were both found to have the characteristic “coat hanger” rib appearance on chest X-ray, raising suspicion for KOS. Molecular testing confirmed KOS in each case. In addition to these new cases, we reviewed the existing cases reported in literature. Presence of polyhydramnios, small thorax, curved ribs, and abdominal wall defects must alert the perinatologist toward the possibility of KOS to facilitate appropriate molecular testing. The overall prognosis of KOS remains poor. Early diagnosis allows for counseling by a multidisciplinary team and enables parents to make informed decisions regarding both pregnancy management and postnatal care.

Clinical and MRI findings in two unrelated cats with globoid cell leucodystrophy

Two unrelated male cats, both five months old, were referred for progressive neurological signs characterised by intentional tremors, paraplegia with absence of nociception in the pelvic limbs, weakness, dysmetria with reduced flexor reflex in the thoracic limbs, and bilaterally reduced menace response. MRI, performed by a 0.25 T Esaote Vet Grande, showed diffuse and irregular intramedullary T2 weighted hyperintensity between T3 and L3; these lesions were isointense on T1 weighted images without contrast uptake. In one patient MRI of the brain was obtained and mild cerebellar volume reduction was found. Histological examination of the brain and spinal cord demonstrated myelin loss and perivascular accumulation of periodic acid-Schiff-positive big macrophages. These findings were consistent with globoid cell leucodystrophy, as previously described in cats. Although not specific, in young cats with progressive spinal neurological signs, especially when associated with cerebellar signs, and irregular but diffuse T2 intramedullary hyperintensity and T1 isointensity without contrast uptake, globoid cell leucodystrophy should be suspected.

Is the Mahali mole-rat (Cryptomys hottentotus mahali) a spontaneous or induced ovulator?

The Mahali mole-rat (Cryptomys hottentotus mahali (Roberts, 1913)) is a social, cooperatively breeding subterranean rodent that breeds aseasonally. Only one female in a colony breeds and the remaining females are reproductively suppressed. When the opportunity arises, these non-reproductive females disperse from the natal colony to escape reproductive suppression and pair up with an unrelated male to start a new colony. This study set out to determine whether female Mahali mole-rats are induced or spontaneous ovulators once separated from the reproductive suppression of the breeding female. Fifteen separated females were subjected to three treatments: housed separately without a male (A), allowed chemical, but not physical, contact with a vasectomised male (NPC), and placed in direct contact with a vasectomised male (PC). Urine was collected from all females under each treatment every 2 days for 40 days. Only females housed in the PC treatment exhibited heightened progesterone concentrations and corpora lutea of ovulation in the ovaries. Furthermore, males possessed epidermal spines on the shaft of the penises that may be used to stimulate the cervix of the female during copulation. These findings suggest that the Mahali mole-rat is an induced ovulator.

Simplex Crumbs Homologue 1 Maculopathy Masquerading as Juvenile X-Linked Retinoschisis in Male Patients

Purpose: We demonstrate that Crumbs homologue 1 ( CRB1) maculopathy should be considered in the differential of petaloid pigmentary changes in the macula of young children with good vision who may be asymptomatic. Methods: We report on 2 unrelated male patients presenting at a young age with decreased vision from a macular dystrophy due to biallelic CRB1 mutations. Results: In addition to a previously described pathogenic variant, Ile167Gly169del, 2 new pathogenic missense variants in CRB1, Thr745Met and Cys948Tyr, are reported here. Conclusions: Although CRB1 mutations have been more commonly described in retinitis pigmentosa and Leber congenital amaurosis, we demonstrate that mutations in CRB1 can cause a maculopathy in which initial features can resemble juvenile X-linked retinoschisis. We show that the accompanying macular edema is responsive to carbonic anhydrase inhibitors. With long-term follow-up for each case, we illustrate the natural history of CRB1 maculopathy based on clinical examination and diagnostic imaging.

Urine-Filled Large Prostatic Cystic Structure in Two Unrelated Male Miniature Dachshunds

ABSTRACT A 1 yr old intact male miniature dachshund presented for posturing to urinate without voiding and nocturia. Physical examination revealed congenital reproductive abnormalities and a fluid-filled structure caudal to the urinary bladder. The dog was diagnosed with a prostatic cyst and underwent an exploratory laparotomy with an attempt to remove the cyst. Twelve weeks later, the dog returned with recurring clinical signs, and the cyst was found to have returned back to its original size. A second intact male miniature dachshund presented at 7 mo of age for stranguria. Physical examination revealed congenital reproductive abnormalities and a fluid-filled structure on rectal palpation, much like the first dog. The dog was diagnosed with a prostatic cyst and underwent an exploratory laparotomy. An attempt was made to close communication between the prostate and cyst. The dog re-presented 3 wk later for recurrence of clinical signs, and the prostatic cyst was found to have increased in size. Both dogs were euthanized because of recurrence of clinical signs. This report describes the presence of prostatic cysts in two young dogs with congenital abnormalities of the genital and reproductive tracts and the similarities seen in human boys diagnosed with prostatic utricles.